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1. Genetic association and gene expression analysis identify FGFR1 as a new susceptibility gene for human obesity

Author: Anne Bouloumié, Karine Clément, Hong Jiao, Dominique Langin, Mikael Rydén, Anders Hamsten, Pilar Galan, Magdalena Taube, Ingrid Dahlman, Anna Benrick, Cyrille Debard, Chantal Simon, Martine Laville, John-Olov Jansson, Angela Silveira, Caroline Hansson, Corneliu Henegar, Tomas Axelsson, Peter Arner, Juha Kere, Hubert Vidal, Karin Dahlman-Wright, Anke Hinney, Niklas Mejhert, Suzanne L. Dickson, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Clinical Research Centre, Karolinska University Hospital [Stockholm], Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-University of Gothenburg ( GU ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Atherosclerosis Research Unit, Karolinska Institutet [Stockholm]-Department of Medicine Solna-Cardiovascular Genetics Group, Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'épidémiologie et de santé publique, Université Louis Pasteur - Strasbourg I, Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of medical sciences, Uppsala University-Molecular Medicine-Science for Life Laboratory, Department of child and adolescent psychiatry, Universität Duisburg-Essen [Essen], Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-University of Gothenburg (GU), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Sahlgrenska Academy at University of Gothenburg [Göteborg], Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Biosciences and Nutrition [Karolinska Insitutet, Sueden] (BioNut), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut National de la Recherche Agronomique (INRA)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Science for Life Laboratory [Solna], Royal Institute of Technology [Stockholm] (KTH ), AFA Insurance, Swedish Heart and Lung Foundation, Swedish Research Council [8691], Novo Nordic Foundation, Swedish Diabetes Association, Knut and Alice Wallenberg Foundation, Stockholm County Council [562183], European Commission [LSHM-CT-2005-018734, ADAPT FP7-Health-2007-A], Direction de la Recherche Clinique/Assistance Publique-Hopitaux de Paris, Programmes Hospitaliers de Recherche Clinique [AOR 02076], Le site de l'Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques, region Ile de France, Swedish Medical Research Council [VR k2007-54x-20328-013], European Union [FP7-HEALTH-2009-241592, FP7-KBBE-2009-3-245009], ALF Goteborg [SU7601], Swedish Foundation for Strategic Research [A305-188], German Ministry of Education and Research (NGFNplus) [01GS0820], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
Subjects: Male, Fibroblast Growth Factor, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Messenger, Medizin, Adipose tissue, Appetite, Biochemistry, Rats, Sprague-Dawley, 0302 clinical medicine, Endocrinology, Odds Ratio, Child, media_common, 2. Zero hunger, 0303 health sciences, education.field_of_study, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Skeletal, Single Nucleotide, Adipose Tissue, Muscle, Female, Western, Type 1, Receptor, Adult, medicine.medical_specialty, Adolescent, Animals, Chi-Square Distribution, European Continental Ancestry Group, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Hypothalamus, Obesity, Polymorphism, RNA, Rats, Sprague-Dawley, media_common.quotation_subject, Population, Blotting, Western, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Context (language use), Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Receptor, Fibroblast Growth Factor, Type 1, education, Muscle, Skeletal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, business.industry, Biochemistry (medical), Odds ratio, Fat cell differentiation, medicine.disease, stomatognathic diseases, business
Abstract: International audience; CONTEXT: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance. OBJECTIVE: Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies. DESIGN: The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus. SETTING: General community and referral centers for specialized care was the setting for the study. PARTICIPANTS: We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats. MAIN OUTCOME MEASURES: We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance. RESULTS: FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 × 10(-6), which was P = 7.0 × 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05). CONCLUSIONS: FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
Published: 2011
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2. Trace elements in glucometabolic disorders: an update

Author: Jean-Robert Rapin, Nicolas Wiernsperger, Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB), BMC, Ed., Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Review, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, medicine, Internal Medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, Biochemical reactions, Glucose homeostasis, In patient, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Beneficial effects, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:RC620-627, 030304 developmental biology, 0303 health sciences, business.industry, medicine.disease, 3. Good health, Trace (semiology), lcsh:Nutritional diseases. Deficiency diseases, business
Abstract: International audience; Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed.
Published: 2010
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3. Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake

Author: Adriana Márquez-Quiñones, Dominique Langin, Karine Clément, Wim H. M. Saris, Teodora Handjieva-Darlenska, Marion Combes, Ping Wang, Andreas Pfeiffer, Dimitris K. Babalis, David M. Mutch, Thomas Meinert Larsen, Susan A. Jebb, Claus Holst, Edwin C. M. Mariman, Hubert Vidal, Arne Astrup, Nathalie Viguerie, Pavla Kalouskova, Balbine Roussel, Cyrille Debard, J. Alfredo Martínez, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Santé Publique et Informatique Médicale (SPIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Human Health and Nutritional Sciences, University of Guelph, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Human Biology, Maastricht University [Maastricht], Institute of Preventive Medicine, Copenhagen University Hospitals, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Pharmacology and Toxicology, Medical Faculty, Medical University, Obesity Management Centre, Institute of Endocrinology, Human Nutrition Research, Elsie Widdowson Laboratory, Department of Internal Medicine, University Hospital of Heraklion, Department of Clinical Nutrition, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], European Community [FP6-513946], Institut National de la Sante et de la Recherche Medicale, Region Midi-Pyrenees, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Santé Publique et Informatique Médicale ( SPIM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Universidad de Navarra [Pamplona] ( UNAV ), Charité Universitäts Medizin Berlin, University of Copenhagen ( KU ), Centre de Recherche en Nutrition Humaine d'Ile-de-France ( CRNH-IDF ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut National Agronomique Paris-Grignon ( INA P-G ) -CETAF-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Paris 13 (UP13)-CETAF-Institut National Agronomique Paris-Grignon (INA P-G)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut de Veille Sanitaire (INVS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humane Biologie, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R1 - Metabolic Syndrome
Subjects: MESH: Treatment Failure, Blood Pressure, MESH: Energy Intake, Transcriptome, 0302 clinical medicine, HIGH-PROTEIN, Models, MESH: Models, Genetic, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, MESH: Treatment Outcome, 0303 health sciences, MACRONUTRIENT, Reducing, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Blood Pressure, MESH: Follow-Up Studies, LOW-FAT, Gene expression profiling, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, LOSS MAINTENANCE, MESH : Adipose Tissue, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Weight Loss, MESH : Treatment Failure, Genetic, Humans, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, Anthropometry, medicine.disease, Obesity, Endocrinology, MICROARRAY DATA, Energy intake, MESH: Female, Calorie, Time Factors, Medicine (miscellaneous), Adipose tissue, MESH : Models, Genetic, HUMAN OBESITY, Weight loss, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : RNA, MESH: Obesity, MESH : Female, Treatment Failure, MESH : Diet, Reducing, 2. Zero hunger, MESH: Diet, Reducing, Nutrition and Dietetics, Reverse Transcriptase Polymerase Chain Reaction, MESH : Adult, ADIPOCYTES, Glycemic index, Treatment Outcome, MESH : Obesity, Female, medicine.symptom, Dieting, MESH : Time Factors, Adult, 030209 endocrinology & metabolism, MESH : Treatment Outcome, Biology, DiOGenes, MESH: RNA, Internal medicine, Weight Loss, medicine, MESH : Blood Pressure, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, LOSS DIETS, Models, Genetic, Gene Expression Profiling, MESH: Time Factors, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, GLYCEMIC INDEX, RNA, MESH : Weight Loss, Energy Intake, Follow-Up Studies
Abstract: Background: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. Objective: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. Design: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. Conclusions: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control. This trial was registered at clinicaltrials.gov as NCT00390637. © 2010 American Society for Nutrition.
Published: 2010
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4. Role of SREBP-1 transcription factors in skeletal muscle function : involvement of the transcriptional repressors BHLHB2 and BHLHB2

Author: Lecomte, Virginie, Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Université Claude Bernard - Lyon I, Étienne Lefai, Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, endocrine system, food and beverages, Muscular atrophy, Insulin-resistance, digestive system, Insulino-résistance, Srebp-1, Différenciation myogénique, polycyclic compounds, Bhlhb2, lipids (amino acids, peptides, and proteins), Myogenic differentiation, Atrophie musculaire, [ SDV.SA ] Life Sciences [q-bio]/Agricultural sciences
Abstract: Transcription factors SREBP-1, Sterol Response Element Binding Proteins, are key regulators of lipid and cholesterol homeostasis. Their function has been largely studied in liver and adipose tissue, but they are also well expressed in skeletal muscle where they mediate insulin transcriptional effects.This work aims to define the muscle specific role of SREBP-1. Microarray analysis of human myotubes over-expressing SREBP-1 identifies more than 1500 SREBP-1 target genes in human skeletal muscle, including number of repressed genes. Gene ontology analysis reveals the involvement of SREBP-1 in a large variety of biological functions in muscle cells. In fact, SREBP-1 represses expression of a number of muscle-specific genes and markers of muscle differentiation. As a result, SREBP-1 over-expression leads to blockage of in vitro myogenic differentiation and marked atrophy in vitro as in Vivo.In the same time, we identified the transcriptional repressors BHLHB2 and BHLHB3 as new direct target genes of SREBP-1, by promoter analysis. 20% of SREBP-1 repressed genes are also target genes of BHLHB2 and BHLHB3. Furthermore, BHLHB2, like SREBP-1, is involved in insulin action on skeletal muscle and muscular insulin-resistance in type 2 diabetic patients.As SREBP-1 effects on atrophy and myogenic differentiation inhibition are reversed by silencing BHLHB2 and BHLHB3 expression, we can conclude that BHLHB2 and BHLHB3 mediate negative SREBP-1action on muscular phenotype.These results confer a new role for SREBP-1 in the regulation of muscle mass and muscle cell differentiation, thus linking the control of muscle mass to metabolic pathways; Les protéines SREBP-1, Sterol Response Element Binding Proteins, sont des régulateurs clés du métabolisme des lipides et du cholestérol. A ce titre, ils ont été largement étudiés dans le foie et le tissu adipeux. Les facteurs SREBP-1 sont également exprimés dans le muscle squelettique au sein duquel ils sont les principaux médiateurs des effets géniques de l’insuline.Les travaux de thèse présentés dans ce manuscrit ont eu pour but de définir le rôle spécifique de SREBP-1 dans le muscle squelettique. L’étude transcriptomique de cellules musculaires humaines révèle plus de1500 gènes régulés par SREBP-1 dans le muscle squelettique humain, dont la moitié est réprimée. L’analyse fonctionnelle de ces gènes révèle l’implication de SREBP-1 dans des fonctions musculaires dépassant la cadre du métabolisme glucido-lipidique. Ainsi, SREBP-1 inhibe l’expression de plusieurs gènes impliqués dans la différenciation et le maintien du phénotype musculaire. En conséquence, la sur expression de SREBP-1 bloque la différenciation myogénique in vitro et induit une atrophie marquée in vitro, sur des myotubes différenciés et in Vivo, dans le muscle squelettique de souris.En parallèle, deux répresseurs transcriptionnels : BHLHB2 et BHLHB3 apparaissent, après étude de leur promoteur, comme deux nouvelles cibles directes de SREBP-1. Ainsi, 20% des gènes inhibés par SREBP-1sont des cibles de BHLHB2 et BHLHB3, de nombreux gènes muscle-spécifiques y compris. De plus, BHLHB2 apparaît, de la même façon que SREBP-1, comme un acteur essentiel dans l’action de l’insuline sur le muscle squelettique, et dans le développement de l’insulino-résistance musculaire chez les patients diabétiques de type2.Le blocage de la différenciation myogénique et l’atrophie induite par SREBP-1 in vitro étant reversées par l’inhibition de l’expression de BHLHB2 et BHLHB3, nous concluons que BHLHB2 et BHLHB3 sont responsables de l’effet répressif de SREBP-1 sur le phénotype musculaire.Ces résultats mettent donc en évidence un nouveau rôle pour les facteurs SREBP-1 dans la régulation de la myogenèse et le maintien de la masse musculaire. SREBP-1 intègrent ainsi la régulation métabolique au contrôle du phénotype musculaire
Published: 2009

5. Blood platelets and human megakaryocytes : effects of different concentrations of docosahexaenoic acid on their activation and redox status

Author: Guillot, Nicolas, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard - Lyon I, Dr. Evelyne Véricel(evelyne, vericel@insa-lyon.fr), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Vericel, Evelyne, Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA )
Subjects: [SDV] Life Sciences [q-bio], plaquettes sanguines ", [ SDV ] Life Sciences [q-bio], genetic structures, "blood cells", "docosahexaenoic acid", [SDV]Life Sciences [q-bio], "acide docosahexaénoïque", "plaquettes sanguines ", acide docosahexaénoïque
Abstract: Docosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid known for its protective effects against cardiovascular disease. However high doses of DHA may nevertheless counteract its beneficial effects owing to the presence of six double bounds in the fatty acyl chain. Our first objective was to determine the effects of increasing DHA consumption by healthy men on both platelet function and oxidative stress. The second objective was to analyse the effects of DHA on gene expression of enzymes controlling redox status and prostanoid formation, using human megakaryocytes MEG-01 as a model of platelet precursors. Our results show that ingestion of low doses of DHA (400 to 1600 mg) decreases the platelet aggregation response. A lower dose shows an anti-oxidant action. This result is reinforced by the transcriptional effects obtained on MEG-01 cells. Our results could explain the beneficial influence of n-3 polyunsaturated fatty acids at low doses on cardiovascular diseases., L'acide docosahexaénoïque (DHA) est un acide gras polyinsaturé n-3 connu pour son rôle protecteur contre les maladies cardiovasculaires. Cependant une utilisation importante de DHA peut néanmoins contrebalancer les effets bénéfiques par la formation de produits d'oxydation dommageables. Notre travail a été de déterminer les effets de l'ingestion de doses croissantes de DHA chez l'Homme sain sur les fonctions, le métabolisme et l'état redox des plaquettes sanguines et d'analyser son action sur un modèle de précurseurs des plaquettes, la lignée humaine de mégacaryocytes MEG-01. Nos résultats montrent que l'ingestion de faibles doses de DHA (400 à 1600 mg) diminue la réponse plaquettaire. Une dose plus faible montre un effet anti-oxydant. Ceci est conforté par les effets transcriptionnels obtenus sur les cellules MEG-01. Ceci pourrait contribuer à l'explication de l'influence bénéfique des acides gras polyinsaturés n-3 à faible dose sur les maladies cardio-vasculaires.
Published: 2008

6. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women

Author: Claus Holst, Nathalie Vega, Moira A. Taylor, J. Alfredo Martínez, Eva Klimcakova, Thorkild I. A. Sørensen, Dominique Langin, Sébastien Déjean, Jean M. Oppert, Peter Arner, Hubert Vidal, Nathalie Viguerie, Karine Clément, Frédéric Capel, Wim H. M. Saris, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les obésités, CHU Toulouse [Toulouse]-Laboratoire, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Lyon-Sud, FACULTE DE LYON, Centre de Recherche en Nutrition Humaine, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Midicine Karolinska Institute, Karolinska University Hospital Huddinge, Department of Sports Medicine of Charles University, Faculty of Medicine Charles University, Department of Physiology and nutrition University of Navarra, Universidad de Navarra [Pamplona] (UNAV), Department of Human Biology Nutrition and Toxicology Research Institute, Maastricht University [Maastricht], The Netherlands Institute of Preventive Medicine, Institute of Preventive Medicine, School of Biomedical Sciences Queen's Medical Center, University of Nottingham Medical School, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Nutrition and Endocrinology AP / HP, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR 31 Louis Bugnard ( IFR 31 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Navarra [Pamplona] ( UNAV ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transcription, Genetic, Endocrinology, Diabetes and Metabolism, MESH: Energy Intake, Biochemistry, Body Mass Index, 0302 clinical medicine, Endocrinology, Gene expression, MESH: Genetic Variation, MESH : Adaptor Proteins, Signal Transducing, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Addipose tissue, Reducing, MESH: Mitochondrial Proteins, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, Body Composition, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, MESH : Body Composition, MESH : Adipose Tissue, MESH: Body Mass Index, MESH : Receptors, Glucocorticoid, 03 medical and health sciences, MESH: Weight Loss, Genetic, Humans, MESH : Fatty Acid-Binding Proteins, MESH : Mitochondrial Proteins, MESH: Adaptor Proteins, Signal Transducing, MESH: Humans, MESH : Humans, Signal Transducing, Genetic Variation, MESH: Adult, Autophagy-Related Protein 8 Family, MESH: Body Composition, medicine.disease, Obesity, MESH : Energy Metabolism, MESH : Body Mass Index, Energy intake, Body mass index, MESH: Female, Candidate gene, MESH: Receptors, Glucocorticoid, Clinical Biochemistry, Adipose tissue, Blood lipids, Glucocorticoid, Weight loss, Sirtuin 3, Receptors, MESH : RNA, Sirtuins, MESH: Obesity, MESH : Female, Nutrición y dietética [Ciencias de la Salud], MESH : Diet, Reducing, 2. Zero hunger, MESH : Sirtuins, MESH: Diet, Reducing, Microfilament Proteins, MESH: Energy Metabolism, Adaptor Proteins, MESH : Adult, MESH: Sirtuins, MESH : Obesity, Female, medicine.symptom, Transcription, Adult, MESH : Microfilament Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, Fatty Acid-Binding Proteins, MESH: Fatty Acid-Binding Proteins, Mitochondrial Proteins, MESH: Microfilament Proteins, Receptors, Glucocorticoid, MESH : Genetic Variation, MESH: RNA, Internal medicine, Weight Loss, medicine, 030304 developmental biology, Adaptor Proteins, Signal Transducing, MESH: Transcription, Genetic, Biochemistry (medical), MESH : Transcription, Genetic, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, RNA, MESH : Weight Loss, Energy Intake, Energy Metabolism
Abstract: Context: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. Objective: We investigated adipose tissue gene expression from human obese women according to energy deficit and, the fat and carbohydrate content of the diet. Design & setting: Obese subjects recruited among 8 European clinical centers followed 10 weeks of either a low fat (high carbohydrate) or a moderate fat (low carbohydrate) hypoenergetic diet. Subjects: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. Main Outcome Measure: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. Results: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. A thousand genes were regulated by energy restriction. We validated an effect of the fat-to-carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA and GABARAPL2) with increased expression during the moderate fat diet. Conclusions: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response. AD - INSERM, U858, Laboratoire de Recherches sur les Obesites, Institut de Medecine Moleculaire de Rangueil, Toulouse; Universite Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse; Centre Hospitalier Universitaire de Toulouse, France; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; INSERM, UMR -870; INRA U-1235; Faculte de Medecine Lyon-Sud universite de Lyon 1; Centre de Recherche en Nutrition Humaine, Hospices civils de Lyon; Lyon, France; Institut de Mathematiques de Toulouse UMR 5219, Universite Paul-Sabatier, Toulouse, France; Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain; Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands; Institute of Preventive Medicine, Centre for Health and Society, Copenhagen University Hospital, Copenhagen, Denmark; School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham Medical School, Nottingham, United Kingdom; INSERM, Nutriomique U872 (Team 7), 75004 Paris, France; Universites Pierre et Marie Curie-Paris6, UMR-S 872, Cordelier Research Center & Paris Descartes, 75006 Paris; and Assistance Publique/Hopitaux de Paris (AP-HP), Pitie Salpetriere Hospital, Nutrition and Endocrinology department, 75013 Paris, France.
Published: 2008
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7. DHA supplementation and immune function

Author: Mebarek, Saïda, Ermak, Natalia, Benzaria, Amal, Vicca, Stéphanie, Dubois, Madeleine, Némoz, Georges, Laville, Martine, Lacour, Bernard, Véricel, Evelyne, Lagarde, Michel, Prigent, Annie-France, Service de Diabétologie et Nutrition, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Nutrition Lipidique et Régulation Fonctionnelle du Coeur et des Vaisseaux ( NLRFC ), Institut National de la Recherche Agronomique ( INRA ) -Université Paris-Sud - Paris 11 ( UP11 ), Service de Biochimie A [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), This work was funded by Inserm and a grant from the Groupe Lipides Nutrition (GLN) (2005)., Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Nutrition Lipidique et Régulation Fonctionnelle du Coeur et des Vaisseaux (NLRFC), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche Croissance et signalisation (UMR_S 845), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: mitochondrial membrane potential, oxidized LDL, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, DHA enrichment, food and beverages, lipids (amino acids, peptides, and proteins), interleukin-2, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Dietary intake of long-chain n-3 PUFA has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However, most human studies examined the combined effect of DHA and EPA using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL. Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800, 1600 mg) in a TAG form containing DHA as the only PUFA, for 2 weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400 mg DHA/d. The tetradecanoylphorbol acetate plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400 mg DHA/d, with a maximum after 800 mg intake, and was positively correlated (P < 0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxidized LDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. Oxidized LDL apoptotic effect was significantly attenuated after 400 mg DHA/d and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxidized LDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis.
Published: 2008
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8. Clarification of the oxidation state of cobalt corroles inheterogeneous and homogeneous catalytic reduction of dioxygen

Author: Mohammed Chkounda, Jing Shen, Maya El Ojaimi, Laurent Frémond, Ping Chen, Claude P. Gros, Shunichi Fukuzumi, Kei Ohkubo, Roger Guilard, Karl M. Kadish, Jean-Michel Barbe, University of Houston, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC), Osaka University [Osaka], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), and Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Porphyrins, Inorganic chemistry, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Redox, Medicinal chemistry, Catalysis, Inorganic Chemistry, [ CHIM.CATA ] Chemical Sciences/Catalysis, chemistry.chemical_compound, corrole, Oxidation state, Electrochemistry, Organometallic Compounds, Perchloric acid, Physical and Theoretical Chemistry, Corrole, Electrodes, ComputingMilieux_MISCELLANEOUS, Perchlorates, 010405 organic chemistry, Electron Spin Resonance Spectroscopy, [CHIM.CATA]Chemical Sciences/Catalysis, cobalt, catalytic reduction of dioxygen, 0104 chemical sciences, Oxygen, Benzonitrile, chemistry, Radical ion, Spectrophotometry, Ultraviolet, Cyclic voltammetry, Oxidation-Reduction, Cobalt
Abstract: Co(III) corroles were investigated as efficient catalysts for the reduction of dioxygen in the presence of perchloric acid in both heterogeneous and homogeneous systems. The investigated compounds are (5,10,15-tris(pentafluorophenyl)corrole)cobalt (TPFCor)Co, (10-pentafluorophenyl-5,15-dimesitylcorrole)cobalt (F 5PhMes 2Cor)Co, and (5,10,15-trismesitylcorrole)cobalt (Mes 3Cor)Co, all of which contain bulky substituents at the three meso positions of the corrole macrocycle. Cyclic voltammetry and rotating ring-disk electrode voltammetry were used to examine the catalytic activity of the compounds when adsorbed on the surface of a graphite electrode in the presence of 1.0 M perchloric acid, and this data is compared to results for the homogeneous catalytic reduction of O 2 in benzonitrile containing 10 (-2) M HClO 4. The corroles were also investigated as to their redox properties in nonaqueous media. A reversible one-electron oxidation occurs at E 1/2 values between 0.42 and 0.89 V versus SCE depending upon the solvent and number of fluorine substituents on the compounds, and this is followed by a second reversible one-electron abstraction at E 1/2 = 0.86 to 1.18 V in CH 2Cl 2, THF, or PhCN. Two reductions of each corrole are also observed in the three solvents. A linear relationship is observed between E 1/2 for oxidation or reduction and the number of electron-withdrawing fluorine groups on the compounds, and the magnitude of the substituent effect is compared to what is observed in the case of tetraphenylporphyrins containing meso -substituted C 6F 5 substituents. The electrochemically generated forms of the corrole can exist with Co(I), Co(II), or Co(IV) central metal ions, and the site of the electron-transfer in each oxidation or reduction of the initial Co(III) complex was examined by UV-vis spectroelectrochemistry. ESR characterization was also used to characterize singly oxidized (F 5PhMes 2Cor)Co, which is unambiguously assigned as a Co(III) radical cation rather than the expected Co(IV) corrole with an unoxidized macrocyclic ring.
Published: 2008
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9. Evidence for a transfer of phospholipids from very low density lipoproteins to platelets. Specific interest in type 2 diabetes

Author: Ibrahim , Salam, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard - Lyon I, Dr Gabriel PONSIN(gabriel.ponsin@insa-lyon.fr), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA )
Subjects: [ SDV ] Life Sciences [q-bio], diabetes, Lipoproteins, [SDV]Life Sciences [q-bio], platelets, phospholipides, Lipoprotéines, lipids (amino acids, peptides, and proteins), plaquettes, phospholipids, diabète
Abstract: Phospholipids play important roles in cell metabolism and signal transduction. In platelets, they are necessary to the development of platelet activation processes. Their hydrolysis necessitates their permanent regeneration. In the present work, we considered the possibility that phospholipids could be transferred from very-low density lipoproteins (VLDL) to platelets. Our work was organized in three stages. Firstly, we have shown that PL transfer was stimulated by platelet activation and by the lipoprotein lipase- mediated lipolysis of VLDL.Secondly, using a series of metabolic inhibitors we have demonstrated that the phospholipid transfer to platelets was dependent upon the activity of cytosolic phospholipase A2.Finally, we studied the putative abnormalities of this transfer in the specific context of type 2 diabetes. We characterized several alterations that could participate to the platelet hyperactivation process observed in this pathology.; Les phospholipides jouent un rôle essentiel dans la signalisation cellulaire. Dans les plaquettes sanguines, ils sont nécessaires à la mise en oeuvre des mécanismes d'activation au cours desquels ils sont hydrolysés. La pérennité de la fonction plaquettaire implique donc un apport permanent de phospholipides. Dans le présent travail, nous avons étudié la possibilité que cet apport pouvait résulter d'un transfert de phospholipides des lipoprotéines de très basse densité (VLDL) aux plaquettes. Dans un premier temps, nous avons montré que ce transfert est stimulé in vitro par l'activation plaquettaire ainsi que par la lipolyse des VLDL induite par la lipoprotéine lipase. Ensuite, nous avons rapporté, grâce à une série expérimentale impliquant divers inhibiteurs métaboliques, que le transfert des PL aux plaquettes dépendait de l'activité de la phospholipase A2 cytosolique. Enfin, nous avons analysé les anomalies de ce transfert dans le diabète de type 2, et montré l'incidence qu'elles pouvaient avoir sur l'hyperactivation plaquettaire caractéristique de cette pathologie.
Published: 2007

10. Efficacy of Diabeloop closed‐loop to improve glycaemic control in patients with type 1 diabetes exposed to copious dinners or to sustained physical exercise

Author: Hanaire, Hélène, Franc, Sylvia, Borot, Sophie, Penfornis, Alfred, Benhamou, Pierre‐Yves, Schaepelynck, Pauline, Renard, Eric, Guerci, Bruno, Jeandidier, Nathalie, Simon, Chantal, Hannaert, Patrick, Xhaard, Ilham, Doron, Maeva, Huneker, Erik, Charpentier, Guillaume, Reznik, Yves, Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Diabétologie, Hôpital Sud Francilien Corbeil Essonne, Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), DIABELOOP S.A., Centre d'études et de recherches pour l'intensification du traitement du diabète (CERITD), Service d'endocrinologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Diabétologie - Maladies Métaboliques - Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Eloi, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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11. Matrix vesicles from chondrocytes and osteoblasts: their biogenesis, properties, functions and biomimetic models

Author: Joanna Bandorowicz Pikula, Karen L. Anderson, Massimo Bottini, Pietro Ciancaglini, David Magne, Ana Maria Simao, Dorit Hanein, Agnieszka Strzelecka-Kiliszek, Lukasz Bozycki, René Buchet, Saida Mebarek, Maytê Bolean, José Luis Millán, Niels Volkmann, Slawomir Pikula, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Mid Sweden University, Nencki Institute of Experimental Biology, Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Sanford Burnham Prebys Medical Discovery Institute, Sanford Burnham Medical Research Institute, La Jolla, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Proteoliposomes, [SDV]Life Sciences [q-bio], Proteomics, Biochemistry, Mineralization (biology), Atomic force microscopy, 0302 clinical medicine, Biomimetic Materials, Models, Apatites, Matrix vesicles, Lipid raft, ComputingMilieux_MISCELLANEOUS, Minerals, Organelle Biogenesis, Chemistry, Vesicle, Calcinosis, Extracellular Matrix, Cell biology, 030220 oncology & carcinogenesis, Intramembranous ossification, Collagen, Mineralization, Proteolipids, Biophysics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Models, Biological, Article, Calcification, Specimen Handling, Extracellular Vesicles, 03 medical and health sciences, Calcification, Physiologic, Chondrocytes, Membrane Microdomains, COLÁGENO, Lipidomics, Electron microscopy, Animals, Humans, Settore BIO/10, Physiologic, Vascular Calcification, Molecular Biology, Endochondral ossification, Hypertrophy, Osteoblasts, Biological, 030104 developmental biology, Biogenesis
Abstract: BACKGROUND: Matrix vesicles (MVs) are released from hypertrophic chondrocytes and from mature osteoblasts, the cells responsible for endochondral and membranous ossification. Under pathological conditions, they can also be released from cells of non-skeletal tissues such as vascular smooth muscle cells. MVs are extracellular vesicles of approximately 100–300 nm diameter harboring the biochemical machinery needed to induce mineralization. SCOPE OF THE REVIEW: The review comprehensively delineates our current knowledge of MV biology and highlights open questions aiming to stimulate further research. The review is constructed as a series of questions addressing issues of MVs ranging from their biogenesis and functions, to biomimetic models. It critically evaluates experimental data including their isolation and characterization methods, like lipidomics, proteomics, transmission electron microscopy, atomic force microscopy and proteoliposome models mimicking MVs. MAJOR CONCLUSIONS: MVs have a relatively well-defined function as initiators of mineralization. They bind to collagen and their composition reflects the composition of lipid rafts. We call attention to the as yet unclear mechanisms leading to the biogenesis of MVs, and how minerals form and when they are formed. We discuss the prospects of employing upcoming experimental models to deepen our understanding of MV-mediated mineralization and mineralization disorders such as the use of reconstituted lipid vesicles, proteoliposomes and, native sample preparations and high-resolution technologies. GRAPHICAL ABSTRACT LEGEND: Matrix vesicles are extracellular vesicles that bind to collagen and can induce formation of apatitic mineral during physiological and ectopic mineralization. Lipid and protein compositions in matrix vesicles resemble those of lipid rafts. Mechanisms of the biogenesis of matrix vesicles and processes leading to mineral/apatite formation are still unclear. Proteoliposomes can serve as biomimetic models to understand matrix vesicle-mediated mineralization.
Published: 2018
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12. Investigating disparities in spatial accessibility to and characteristics of sport facilities: Direction, strength, and spatial scale of associations with area income

Author: Arnaud Banos, Jean-Michel Oppert, Hélène Charreire, Christiane Weber, Nathalie Billaudeau, Chantal Simon, Paul Salze, Dominique Badariotti, Romain Casey, Basile Chaix, ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Laboratoire Image, Ville, Environnement [Strasbourg] (LIVE), Université de Strasbourg (UNISTRA), French National Research Agency (Agence Nationale de la Recherche) [ANR-07-PNRA-004], Ile-de-France Regional and Departmental Youth and Sports Direction, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital de l'Hôtel-Dieu, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Paris, Health (social science), Resource (biology), Geography, Planning and Development, sport facilities, Physical activity, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, residential characteristics, Environmental health, Humans, 030212 general & internal medicine, Socioeconomics, Sensitivity analyses, Environmental justice, 030505 public health, Geography, Public Health, Environmental and Occupational Health, Health Status Disparities, [SHS.GEO]Humanities and Social Sciences/Geography, Census, income, Socioeconomic Factors, 13. Climate action, Geographic analysis, Spatial ecology, 0305 other medical science, geographic analysis, Sports
Abstract: We conducted an environmental justice study of the spatial distribution of sport facilities, a major resource for physical activity, in the Paris Region in France. Comprehensive data of the French Census of Sport Facilities allowed us to investigate disparities not only in the spatial accessibility to facilities, but also in the characteristics of these facilities. We found that the associations between area income and the presence of facilities or favorable characteristics of these facilities varied from positive to negative depending on the facilities and on the characteristics examined. Sensitivity analyses defining area income in circular areas of different radii permitted a redined identification of areas underserved in sport facilities.
Published: 2011
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13. The [1-13C]acetate recovery factor to correct tracer-derived dietary fat oxidation is lower in overweight insulin-resistant subjects

Author: Clément Villars, Carine Platat, Edwina Antoun, Audrey Bergouignan, Dale A. Schoeller, Iman Momken, Stéphane Blanc, Chantal Simon, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de médecine (EA1801), Department of Nutritional Sciences, University of Wisconsin-Madison, National Program in Human Nutrition (INSERM and INRA), Fondation Coeur et Artères, Fondation Louis D., Hôpitaux Universitaires de Strasbourg, and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, business.industry, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Endocrinology, Diabetes and Metabolism, Physical activity, stable isotopes, Insulin resistant, exogenous fatty acid oxidation, Overweight, Fasting insulin, Fat mass, Endocrinology, Internal medicine, [SDE]Environmental Sciences, Basal metabolic rate, Medicine, medicine.symptom, business, Beta oxidation, Dietary fat, mass spectrometry
Abstract: International audience; Background&aims: An acetate recovery factor (ARF) is utilized to correct tracer-derived fat oxidation when 13C is used. We showed that when 13C labelled fatty acid are given orally, dietary fat oxidation can be accurately corrected by using an averaged dietary ARF (dARF) derived from 56 lean healthy subjects, instead of individual dARF. The extent to which this factor is valid in overweight insulin resistant subjects is unknown. Methods: [1-13C]dARF and [1-13C]fatty acid recoveries were assessed before and after physical activity/ inactivity interventions in overweight insulin-resistant (n ¼ 11) and lean subjects (n ¼ 70) in five studies herein compiled. Results: Overweight dARF was lower compared to lean subjects (45.3 1.5% vs. 50.6 0.6%; P ¼ 0.002). Physical activity intervention did not impact dARF. dARF correlated negatively with %body fat (r2 ¼ 0.10; P ¼ 0.005) and fasting insulin to glucose ratio (r2 ¼ 0.08; P ¼ 0.02). Applying the lean average [1-13C] dARF induced an 11.5% (P ¼ 0.006) average error in fatty acid oxidation rate. Conclusions: Overweight insulin resistant subjects have lower dARF than lean individuals. An average dARF derived from lean subjects cannot be applied in overweight subjects to calculate dietary fat oxidation. We recommend that individual dARF are measured in subjects with metabolic disorders
Published: 2010
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14. Measuring the food environment using geographical information systems: a methodological review

Author: Chantal Simon, Romain Casey, Arnaud Banos, Paul Salze, Basile Chaix, Dominique Badariotti, Jean-Michel Oppert, Christiane Weber, Hélène Charreire, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire Image, Ville, Environnement [Strasbourg] (LIVE), Université de Strasbourg (UNISTRA), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital de l'Hôtel-Dieu, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut National de la Recherche Agronomique (INRA), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA)
Subjects: PubMed, Restaurants, Geographic information system, Computer science, Medicine (miscellaneous), Transportation, 030209 endocrinology & metabolism, PsycINFO, Environment, MEDLARS, Geographical Information System, Food Supply, Food Preferences, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, GeoBase (geospatial data), Information system, Humans, 030212 general & internal medicine, food environment, 2. Zero hunger, Nutrition and Dietetics, business.industry, digestive, oral, and skin physiology, Public Health, Environmental and Occupational Health, Mode (statistics), [SHS.GEO]Humanities and Social Sciences/Geography, Nutrition Surveys, Flow network, Data science, Field (geography), Food, Geographic Information Systems, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Network analysis
Abstract: ObjectiveThrough a literature review, we investigated the geographic information systems (GIS) methods used to define the food environment and the types of spatial measurements they generate.DesignReview study.SettingSearches were conducted in health science databases, including Medline/Pubmed, PsycINFO, Francis and GeoBase. We included studies using GIS-based measures of the food environment published up to 1 June 2008.ResultsTwenty-nine papers were included. Two different spatial approaches were identified. The density approach quantifies the availability of food outlets using the buffer method, kernel density estimation or spatial clustering. The proximity approach assesses the distance to food outlets by measuring distances or travel times. GIS network analysis tools enable the modelling of travel time between referent addresses (home) and food outlets for a given transportation network and mode, and the assumption of travel routing behaviours. Numerous studies combined both approaches to compare food outlet spatial accessibility between different types of neighbourhoods or to investigate relationships between characteristics of the food environment and individual food behaviour.ConclusionsGIS methods provide new approaches for assessing the food environment by modelling spatial accessibility to food outlets. On the basis of the available literature, it appears that only some GIS methods have been used, while other GIS methods combining availability and proximity, such as spatial interaction models, have not yet been applied to this field. Future research would also benefit from a combination of GIS methods with survey approaches to describe both spatial and social food outlet accessibility as important determinants of individual food behaviours.
Published: 2010
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15. Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle

Author: Etienne Lefai, Vanessa Euthine, Virginie Lecomte, Sophie Rome, Cyrille Debard, Hubert Vidal, Jennifer Rieusset, Emmanuelle Meugnier, meugnier, emmanuelle, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), This work was supported in part by a research grant from the French National Program of Research on Diabetes (PNRD, ROSIH project)., Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vericel, Evelyne, and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: MESH: Oxidation-Reduction, Cell Extracts, Male, Microarray, Physiology, [SDV]Life Sciences [q-bio], MESH: Glycogen, Muscle Fibers, Skeletal, MESH: Base Sequence, MESH: Protein Isoforms, 0302 clinical medicine, Transcription (biology), MESH: Cell Extracts, Protein Isoforms, Gene Regulatory Networks, Promoter Regions, Genetic, transcription factor, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, MESH: Gene Regulatory Networks, Oligonucleotide Array Sequence Analysis, MESH: Chromatin Immunoprecipitation, MESH: Muscle, Skeletal, 0303 health sciences, MESH: Muscle Fibers, Skeletal, MESH: Immunoblotting, adenovirus, MESH: Transcription Factors, MESH: Gene Expression Regulation, MESH: Glucose, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Female, lipids (amino acids, peptides, and proteins), Sterol Regulatory Element Binding Protein 1, Oxidation-Reduction, Glycogen, MESH: Cells, Cultured, Gene isoform, Chromatin Immunoprecipitation, Immunoblotting, Molecular Sequence Data, Biology, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, MESH: Promoter Regions, Genetic, Genetics, Humans, human, RNA, Messenger, skeletal muscle, Muscle, Skeletal, Gene, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, promoter, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Promoter, Molecular biology, MESH: Male, DNA binding motif, Sterol regulatory element-binding protein, DNA binding site, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Glucose, Gene Expression Regulation, MESH: Oligonucleotide Array Sequence Analysis, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Transcription Factors
Abstract: International audience; In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism. Six hundred fifty-two of all genes identified to be differentially regulated on SREBP overexpression had a sterol regulatory element (SRE) motif in their promoter sequences. Among these, 429 were specifically regulated by SREBP-1a, 69 by SREBP-1c, and 154 by both 1a and 1c. Because both isoforms recognize the same binding motif, we determined whether some of these functional differences could depend on the environment of the SRE motifs in the promoters. Results from promoter analysis showed that different combinations of transcription factor binding sites around the SRE binding motifs may determine regulatory networks of transcription that could explain the superposition of lipid and cholesterol metabolism with various other pathways involved in adaptive responses to stress like hypoxia and heat shock, or involvement in the immune response.
Published: 2008
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16. V1a vasopressin receptor expression is modulated during myogenic differentiation

Author: Marta Alessandrini, Valeria De Arcangelis, Monica Alvisi, Mario Molinaro, Sergio Adamo, Valeria Palombi, Georges Némoz, Fabio Naro, Letizia Ciccone, Dipartimento di Istologia ed Embriologia Medica, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Italian Ministry of University (Cofin 2006-2007) and Faculty grants to F.N. and by Progetti di Ateneo and AFM (Pr. 11788) grants to S.A., Vericel, Evelyne, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Roma 'La Sapienza' [Rome]
Subjects: Receptors, Vasopressin, Cancer Research, medicine.medical_specialty, Gene Expression, Stimulation, Biology, Dexamethasone, 03 medical and health sciences, cyclosporine a, dexamethasone, mrna stability, myogenesis, v1ar, 0302 clinical medicine, Internal medicine, medicine, Animals, Myocyte, RNA, Messenger, Rats, Wistar, Receptor, Molecular Biology, Cells, Cultured, DNA Primers, 030304 developmental biology, Vasopressin receptor, 0303 health sciences, Messenger RNA, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Myogenesis, Muscles, VIaR-mRNA stability-myogenesis-cyclosporine A-dexamethasone, Cell Differentiation, Cell Biology, Transfection, Blotting, Northern, Immunohistochemistry, Rats, Cell biology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Azacitidine, Cyclosporine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Fetal bovine serum, Half-Life, Developmental Biology
Abstract: International audience; Neurohypophyseal peptides potently stimulate myogenic differentiation by acting through different receptors of the same family. Here, we show that L6C5 myogenic cells express, at a high density, a single class of V1a Arg8-vasopressin (AVP) receptor. The expression of the vasopressin receptor of type 1a (V1aR) is significantly higher in proliferating myoblasts than in differentiated myotubes. The differentiation-related decrease of V1aR expression was evident both at the mRNA and at the protein level as shown by the reduction of [(3)H]-AVP binding. However, in L6C5 cells transfected with a synthetic construct containing the luciferase gene driven by the 2 kb upstream region of V1aR, we observed a stimulation of the activity of the promoter when the cells were cultured in differentiative medium. The down-regulation of the V1aR correlated with a decreased half-life of its mRNA (half-life 5.86+/-0.74 hr in 10% fetal bovine serum [FBS] versus 3.53+/-0.72 hr in 1% FBS). Cyclosporine A and dexamethasone, but not 5'-azacytidine, treatments of cells in differentiation medium restored the V1aR level to that measured in proliferating L6C5 cells, thus confirming the role of post-transcriptional mechanisms in the modulation of V1aR expression. Taken together, these data show that mRNA stability plays a role in modulating protein expression during the myogenic differentiation process.
Published: 2008
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17. The Gaia-ESO survey: the inner disk intermediate-age open cluster NGC 6802

Author: Gražina Tautvaišienė, P. Donati, Sergey E. Koposov, Sérgio F. Sousa, Gerard Gilmore, F. M. Jiménez-Esteban, C. Munoz, E. Franciosini, O. Snaith, Baitian Tang, Vardan Adibekyan, E. Pancino, R. Ženovienė, Laura Magrini, Lorenzo Monaco, Ettore Flaccomio, G. Carraro, Loredana Prisinzano, Andrew R. Casey, Sofia Randich, John D. Lewis, Carmela Lardo, Roger E. Cohen, Angela Bragaglia, Eileen D. Friel, Tomaz Zwitter, F. Mauro, Rodolfo Smiljanic, M. T. Costado, Arnas Drazdauskas, A. C. Lanzafame, Amelia Bayo, Simone Zaggia, A. Hourihane, C. C. Worley, L. Morbidelli, Sandro Villanova, P. Francois, Douglas Geisler, Rosanna Sordo, Paula Jofre, S. Blanco-Cuaresma, Francesco Damiani, I. San Roman, G. G. Sacco, Andreas Korn, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Departamento de Fisica Teorica C-XI (FTUAM), Universidad Autonoma de Madrid (UAM), INAF - Osservatorio Astronomico di Bologna (OABO), Istituto Nazionale di Astrofisica (INAF), Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Korea Institute for Advanced Study (KIAS), Centro de Astrofísica da Universidade do Porto (CAUP), Universidade do Porto, University of Ljubljana, Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), INAF - Osservatorio Astronomico di Padova (OAPD), Department of Astronomy and Space Physics [Uppsala], Uppsala University, INAF - Osservatorio Astrofisico di Catania (OACT), University of Turin, Ecole Polytechnique Fédérale de Lausanne (EPFL), Istituto Nazionale di Fisica Nucleare, Sezione di Milano (INFN), Istituto Nazionale di Fisica Nucleare (INFN), Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto [Porto], M2A 2017, Laboratoire d'Astrophysique de Bordeaux [Pessac] (LAB), Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS), Osservatorio Astronomico di Bologna (OABO), Istituto Nazionale di Fisica Nucleare [Milano] (INFN), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), European Commission, European Research Council, Leverhulme Trust, Comisión Nacional de Investigación Científica y Tecnológica (Chile), Tang B., Geisler D., Friel E., Villanova S., Smiljanic R., Casey A.R., Randich S., Magrini L., San Roman I., Munoz C., Cohen R.E., Mauro F., Bragaglia A., Donati P., Tautvaisiene G., Drazdauskas A., Zenoviene R., Snaith O., Sousa S., Adibekyan V., Costado M.T., Blanco-Cuaresma S., Jimenez-Esteban F., Carraro G., Zwitter T., Francois P., Jofre P., Sordo R., Gilmore G., Flaccomio E., Koposov S., Korn A.J., Lanzafame A.C., Pancino E., Bayo A., Damiani F., Franciosini E., Hourihane A., Lardo C., Lewis J., Monaco L., Morbidelli L., Prisinzano L., Sacco G., Worley C.C., and Zaggia S.
Subjects: astro-ph.SR, astro-ph.GA, Milky Way, FOS: Physical sciences, Astrophysics, 01 natural sciences, 0103 physical sciences, individual: NGC 6802 [Open clusters and associations], 010303 astronomy & astrophysics, Solar and Stellar Astrophysics (astro-ph.SR), QC, ComputingMilieux_MISCELLANEOUS, QB, [PHYS]Physics [physics], Physics, general [Open clusters and associations], 010308 nuclear & particles physics, open clusters and associations: individual: NGC 6802, open clusters andassociations: general, stars: abundances, Stars: abundances, Astronomy and Astrophysics, Open clusters and associations: general, Open clusters and associations: individual: NGC 6802, Astrophysics - Astrophysics of Galaxies, Radial velocity, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), abundances [Stars], [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Data release, Open cluster
Abstract: Full list of authors: Tang, B.; Geisler, D.; Friel, E.; Villanova, S.; Smiljanic, R.; Casey, A. R.; Randich, S.; Magrini, L.; San Roman, I.; Muñoz, C.; Cohen, R. E.; Mauro, F.; Bragaglia, A.; Donati, P.; Tautvaišien*error*ė, G.; Drazdauskas, A.; Ženovienė, R.; Snaith, O.; Sousa, S.; Adibekyan, V. Costado, M. T.; Blanco-Cuaresma, S.; Jiménez-Esteban, F.; Carraro, G.; Zwitter, T.; François, P.; Jofrè, P.; Sordo, R.; Gilmore, G.; Flaccomio, E.; Koposov, S.; Korn, A. J.; Lanzafame, A. C.; Pancino, E.; Bayo, A.; Damiani, F.; Franciosini, E.; Hourihane, A.; Lardo, C.; Lewis, J.; Monaco, L.; Morbidelli, L.; Prisinzano, L.; Sacco, G.; Worley, C. C.; Zaggia, S., Milky Way open clusters are very diverse in terms of age, chemical composition, and kinematic properties. Intermediate-age and old open clusters are less common, and it is even harder to find them inside the solar Galactocentric radius, due to the high mortality rate and strong extinction inside this region. NGC 6802 is one of the inner disk open clusters (IOCs) observed by the Gaia-ESO survey (GES). This cluster is an important target for calibrating the abundances derived in the survey due to the kinematic and chemical homogeneity of the members in open clusters. Using the measurements from Gaia-ESO internal data release 4 (iDR4), we identify 95 main-sequence dwarfs as cluster members from the GIRAFFE target list, and eight giants as cluster members from the UVES target list. The dwarf cluster members have a median radial velocity of 13.6 ± 1.9 km s, while the giant cluster members have a median radial velocity of 12.0 ± 0.9 km s and a median [Fe/H] of 0.10 ± 0.02 dex. The color-magnitude diagram of these cluster members suggests an age of 0.9 ± 0.1 Gyr, with (m-M) = 11.4 and E(B-V) = 0.86. We perform the first detailed chemical abundance analysis of NGC 6802, including 27 elemental species. To gain a more general picture about IOCs, the measurements of NGC 6802 are compared with those of other IOCs previously studied by GES, that is, NGC 4815, Trumpler 20, NGC 6705, and Berkeley 81. NGC 6802 shows similar C, N, Na, and Al abundances as other IOCs. These elements are compared with nucleosynthetic models as a function of cluster turn-off mass. The α, iron-peak, and neutron-capture elements are also explored in a self-consistent way. © ESO, 2017., Based on data products from observations made with ESO Telescopes at the La Silla Paranal Observatory under programme ID 188.B-3002. These data products have been processed by the Cambridge Astronomy Survey Unit (CASU) at the Institute of Astronomy, University of Cambridge, and by the FLAMES/UVES reduction team at INAF/Osservatorio Astrofisico di Arcetri. These data have been obtained from the Gaia-ESO Survey Data Archive, prepared and hosted by the Wide Field Astronomy Unit, Institute for Astronomy, University of Edinburgh, which is funded by the UK Science and Technology Facilities Council. This work was partly supported by the European Union FP7 programme through ERC grant number 320360 and by the Leverhulme Trust through grant RPG-2012-541. We acknowledge the support from INAF and Ministero dell' Istruzione, dell' Universita e della Ricerca (MIUR) in the form of the grant "Premiale VLT 2012". The results presented here benefit from discussions held during the Gaia-ESO workshops and conferences supported by the ESF (European Science Foundation) through the GREAT Research Network Programme. We thank the anonymous referee for insightful comments. D.G., S.V., and B.T. gratefully acknowledges support from the Chilean BASAL Centro de Excelencia en Astrofisica y Tecnologias Afines (CATA) grant PFB-06/2007. C.M. acknowledges support from CONICYT-PCHA/Doctorado Nacional/2014-21141057. R.E.C. acknowledges funding from Gemini-CONICYT for Project 32140007. F.M. gratefully acknowledges the support provided by Fondecyt for project 314017. This work was partly supported (A.R.C.) by the European Union FP7 programme through grant number 320360. This work was partly supported (A.D., G.T., R.Z.) by the grant from the Research Council of Lithuania (MIP082/2015). S.G.S. acknowledges the support from FCT through Investigador FCT contract of reference IF/00028/2014 and the support from FCT through the project PTDC/FIS-AST/7073/2014. C.L. gratefully acknowledges financial support from the European Research Council (ERC-CoG-646928, Multi-Pop, PI: N. Bastian). V.A. acknowledges the support from the FCT (Portugal) in the form of the grant SFRH/BPD/70574/2010, the support by FCT through national funds (Refs. PTDC/FIS-AST/7073/2014 and PTDC/FIS-AST/1526/2014) and by FEDER through COMPETE2020 (Refs. POCI-01-0145-FEDER-016880 and POCI-01-0145-FEDER-016886).
Published: 2017
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18. A new facile preparation of a bifunctionalized C6 homologating agent from 1,4-cyclohexadiene

Author: Chevallier-Michaud, Sabine, Michaud, Sabine, Viala, Jacques, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and CHEVALLIER-MICHAUD, SABINE
Subjects: 010405 organic chemistry, Organic Chemistry, Acetal, 010402 general chemistry, 01 natural sciences, Biochemistry, 0104 chemical sciences, chemistry.chemical_compound, chemistry, [CHIM] Chemical Sciences, Drug Discovery, [CHIM]Chemical Sciences, Organic chemistry, 1,4-Cyclohexadiene, ComputingMilieux_MISCELLANEOUS
Abstract: a new preparation of the bifunctionalized unsaturated C6 homologating agent 2b which is an efficient synthetic tool is described. This method is atom economic, very efficient on grams scale and easy to handle from cheap commercially available 1,4-cyclohexadiene. Synthetic applications by using a mild and selective monohydrolysis of acetal catalysed by FeCl3 are described.
Published: 1999
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19. Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids

Author: Camont, Laurent, Lhomme, Marie, Rached, Fabiana, Le Goff, Wilfried, Nègre-Salvayre, Anne, Salvayre, Robert, Calzada, Catherine, Lagarde, Michel, Chapman, M. John, Kontush, Anatol, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de recherche Pau Droit Public (PDP), Université de Pau et des Pays de l'Adour (UPPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Régulations cellulaires: lipidoses et atherosclerose., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2013
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20. Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice.: xanthine oxidase-induced muscle oxidative stress

Author: Bravard, Amélie, Bonnard, Charlotte, Durand, Annie, Chauvin, Marie-Agnès, Favier, Roland, Vidal, Hubert, Rieusset, Jennifer, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Sante et de la Recherche Medicale, National Program on Diabetes Research, Agence Nationale de la Recherche [ANR-09-JCJC-0116-01], Rhones-Alpes Region, and Servier Laboratories (Suresnes, France)
Subjects: MESH: Protein Carbonylation, oxypurinol, EXERCISE, MESH: Insulin, MESH: Xanthine Oxidase, SUPEROXIDE, MESH: Diet, MESH: Mice, Inbred C57BL, MESH: RNA, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Adenosine Triphosphate, MESH: Diabetes Mellitus, Experimental, MESH: Animals, MESH: Mice, IN-VIVO, METABOLIC SYNDROME, reactive oxygen species, MESH: Muscle, Skeletal, NITRIC-OXIDE, MESH: Oxidative Stress, diabetes, MESH: Antioxidants, MESH: Mitochondria, Muscle, INSULIN-RESISTANT MICE, MESH: Oxypurinol, DYSFUNCTION, MESH: Male, mitochondria, MESH: Enzyme Inhibitors, MESH: Microscopy, Electron, Transmission, MESH: Hydrogen Peroxide, FREE-RADICAL PRODUCTION, REACTIVE OXYGEN, NAD(P)H OXIDASE, MESH: Hyperglycemia, MESH: Diabetes Mellitus, Type 1, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Diabetes Mellitus, Type 2
Abstract: International audience; Reactive oxygen species (ROS) have been widely implicated in the pathogenesis of diabetes and more recently in mitochondrial alterations in skeletal muscle of diabetic mice. However, so far the exact sources of ROS in skeletal muscle have remained elusive. Aiming at better understanding the causes of mitochondrial alterations in diabetic muscle, we designed this study to characterize the sites of ROS production in skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Hyperglycemic STZ mice showed increased markers of systemic and muscular oxidative stress, as evidenced by increased circulating H(2)O(2) and muscle carbonylated protein levels. Interestingly, insulin treatment reduced hyperglycemia and improved systemic and muscular oxidative stress in STZ mice. We demonstrated that increased oxidative stress in muscle of STZ mice is associated with an increase of xanthine oxidase (XO) expression and activity and is mediated by an induction of H(2)O(2) production by both mitochondria and XO. Finally, treatment of STZ mice, as well as high-fat and high-sucrose diet-fed mice, with oxypurinol reduced markers of systemic and muscular oxidative stress and prevented structural and functional mitochondrial alterations, confirming the in vivo relevance of XO in ROS production in diabetic mice. These data indicate that mitochondria and XO are the major sources of hyperglycemia-induced ROS production in skeletal muscle and that the inhibition of XO reduces oxidative stress and improves mitochondrial alterations in diabetic muscle.
Published: 2011
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21. Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice

Author: Bravard, Amélie, Bonnard, Charlotte, Durand, Annie, Chauvin, Marie-Agnès, Favier, Roland, Vidal, Hubert, Rieusset, Jennifer, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Sante et de la Recherche Medicale, National Program on Diabetes Research, Agence Nationale de la Recherche [ANR-09-JCJC-0116-01], Rhones-Alpes Region, Servier Laboratories (Suresnes, France), and Vericel, Evelyne
Subjects: MESH: Protein Carbonylation, oxypurinol, EXERCISE, MESH: Insulin, MESH: Xanthine Oxidase, SUPEROXIDE, MESH: Diet, MESH: Mice, Inbred C57BL, MESH: RNA, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Adenosine Triphosphate, MESH: Diabetes Mellitus, Experimental, MESH: Animals, MESH: Mice, IN-VIVO, METABOLIC SYNDROME, reactive oxygen species, MESH: Muscle, Skeletal, NITRIC-OXIDE, MESH: Oxidative Stress, diabetes, MESH: Antioxidants, MESH: Mitochondria, Muscle, INSULIN-RESISTANT MICE, MESH: Oxypurinol, DYSFUNCTION, MESH: Male, mitochondria, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Enzyme Inhibitors, MESH: Microscopy, Electron, Transmission, MESH: Hydrogen Peroxide, FREE-RADICAL PRODUCTION, REACTIVE OXYGEN, NAD(P)H OXIDASE, MESH: Hyperglycemia, MESH: Diabetes Mellitus, Type 1, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Diabetes Mellitus, Type 2
Abstract: International audience; Reactive oxygen species (ROS) have been widely implicated in the pathogenesis of diabetes and more recently in mitochondrial alterations in skeletal muscle of diabetic mice. However, so far the exact sources of ROS in skeletal muscle have remained elusive. Aiming at better understanding the causes of mitochondrial alterations in diabetic muscle, we designed this study to characterize the sites of ROS production in skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Hyperglycemic STZ mice showed increased markers of systemic and muscular oxidative stress, as evidenced by increased circulating H(2)O(2) and muscle carbonylated protein levels. Interestingly, insulin treatment reduced hyperglycemia and improved systemic and muscular oxidative stress in STZ mice. We demonstrated that increased oxidative stress in muscle of STZ mice is associated with an increase of xanthine oxidase (XO) expression and activity and is mediated by an induction of H(2)O(2) production by both mitochondria and XO. Finally, treatment of STZ mice, as well as high-fat and high-sucrose diet-fed mice, with oxypurinol reduced markers of systemic and muscular oxidative stress and prevented structural and functional mitochondrial alterations, confirming the in vivo relevance of XO in ROS production in diabetic mice. These data indicate that mitochondria and XO are the major sources of hyperglycemia-induced ROS production in skeletal muscle and that the inhibition of XO reduces oxidative stress and improves mitochondrial alterations in diabetic muscle.
Published: 2011
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22. Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis in response to anti-TNF-alpha treatments

Author: Hubert Vidal, Jacques Tebib, Fabienne Coury, Emmanuelle Meugnier, Jean Sibilia, Sophie Rome, Nicole Fabien, Jacques Bienvenu, Carole Ferraro-Peyret, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]
Subjects: Male, MESH: Antirheumatic Agents, Physiology, [SDV]Life Sciences [q-bio], Arthritis, LYMPHOCYTES, Polymerase Chain Reaction, DISEASE, Receptors, Tumor Necrosis Factor, Etanercept, MESH: Antibodies, Monoclonal, Pathogenesis, ACTIVATION, Arthritis, Rheumatoid, 0302 clinical medicine, JUVENILE IDIOPATHIC ARTHRITIS, ComputingMilieux_MISCELLANEOUS, TUMOR-NECROSIS-FACTOR, Oligonucleotide Array Sequence Analysis, MESH: Immunoglobulin G, 0303 health sciences, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, Antibodies, Monoclonal, Middle Aged, 3. Good health, Rheumatoid arthritis, Antirheumatic Agents, Female, Antibody, medicine.symptom, medicine.drug, Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, KAPPA-B, Biology, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, MESH: Gene Expression Profiling, Genetics, medicine, Adalimumab, Humans, 030304 developmental biology, 030203 arthritis & rheumatology, MONONUCLEAR-CELLS, MESH: Humans, THERAPEUTIC TARGET, Tumor Necrosis Factor-alpha, P-SELECTIN, SYNOVIAL-FLUIDS, Gene Expression Profiling, MESH: Adult, MESH: Polymerase Chain Reaction, medicine.disease, MESH: Receptors, Tumor Necrosis Factor, MESH: Male, Gene expression profiling, anti-TNF-alpha therapies, Mechanism of action, MESH: Antibodies, Monoclonal, Humanized, MESH: Tumor Necrosis Factor-alpha, Immunoglobulin G, Immunology, MESH: Oligonucleotide Array Sequence Analysis, biology.protein, MESH: Female
Abstract: International audience; The efficacy of anti-TNF-α therapies highlights the role of TNF-α in the pathogenesis of rheumatoid arthritis (RA). However, the mechanism of action of these agents is poorly understood at the molecular level. The aim of this study was to characterize the effects of anti-TNF-α treatment on the global gene expression profile in peripheral blood mononuclear cells (PBMCs) of responder RA patients. Changes in gene expression were determined using oligonucleotide microarrays (25,341 genes) in PBMCs obtained before and after 12 wk of treatment with either etanercept or adalimumab from responder RA patients. Two hundred fifty-one genes displayed significant changes (false discovery rate < 0.1%) in expression level (178 upregulations with mean fold change = 1.5 and 73 downregulations with mean fold change = -1.50) after 12 wk of treatment. Importantly, the expression of several genes, including those coding for the calcium binding proteins S100A12 and A8, CD14 antigen, Selectin P, or ribosomal protein L39, reported to be upregulated in RA patients, were found to be decreased after anti-TNF-α treatment. Globally, inflammation, immune response, apoptosis, protein synthesis, and mitochondrial oxido-reduction were the most affected pathways in response to anti-TNF-α treatment. The obtained gene expression signature in PBMCs provides new information to better understand the mechanisms of action of anti-TNF-α treatment in RA patients.
Published: 2011
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23. Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice

Author: Jennifer Rieusset, Marie-Agnès Chauvin, C. Bonnard, Hubert Vidal, Annie Durand, Amélie Bravard, Roland Favier, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Sante et de la Recherche Medicale, National Program on Diabetes Research, Agence Nationale de la Recherche [ANR-09-JCJC-0116-01], Rhones-Alpes Region, and Servier Laboratories (Suresnes, France)
Subjects: Male, Physiology, Endocrinology, Diabetes and Metabolism, Mitochondrion, medicine.disease_cause, Antioxidants, Pathogenesis, Protein Carbonylation, chemistry.chemical_compound, Mice, 0302 clinical medicine, Adenosine Triphosphate, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Adenosine Triphosphate, MESH: Diabetes Mellitus, Experimental, Insulin, MESH: Animals, Enzyme Inhibitors, IN-VIVO, METABOLIC SYNDROME, reactive oxygen species, chemistry.chemical_classification, MESH: Muscle, Skeletal, 0303 health sciences, MESH: Oxidative Stress, diabetes, Reverse Transcriptase Polymerase Chain Reaction, MESH: Mitochondria, Muscle, 3. Good health, mitochondria, medicine.anatomical_structure, MESH: Enzyme Inhibitors, MESH: Microscopy, Electron, Transmission, MESH: Hydrogen Peroxide, FREE-RADICAL PRODUCTION, NAD(P)H OXIDASE, MESH: Diabetes Mellitus, Type 1, MESH: Diabetes Mellitus, Type 2, MESH: Protein Carbonylation, medicine.medical_specialty, Xanthine Oxidase, Oxypurinol, EXERCISE, MESH: Insulin, Biology, MESH: Xanthine Oxidase, Diabetes Mellitus, Experimental, SUPEROXIDE, 03 medical and health sciences, MESH: Diet, Microscopy, Electron, Transmission, MESH: Mice, Inbred C57BL, MESH: RNA, Physiology (medical), Internal medicine, Diabetes mellitus, medicine, Animals, Xanthine oxidase, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, Reactive oxygen species, NITRIC-OXIDE, MESH: Antioxidants, Skeletal muscle, Hydrogen Peroxide, Xanthine, medicine.disease, INSULIN-RESISTANT MICE, MESH: Oxypurinol, DYSFUNCTION, MESH: Male, Diet, Mitochondria, Muscle, Mice, Inbred C57BL, Oxidative Stress, Endocrinology, Diabetes Mellitus, Type 1, chemistry, Diabetes Mellitus, Type 2, Hyperglycemia, RNA, REACTIVE OXYGEN, MESH: Hyperglycemia, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Oxidative stress
Abstract: Reactive oxygen species (ROS) have been widely implicated in the pathogenesis of diabetes and more recently in mitochondrial alterations in skeletal muscle of diabetic mice. However, so far the exact sources of ROS in skeletal muscle have remained elusive. Aiming at better understanding the causes of mitochondrial alterations in diabetic muscle, we designed this study to characterize the sites of ROS production in skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Hyperglycemic STZ mice showed increased markers of systemic and muscular oxidative stress, as evidenced by increased circulating H2O2 and muscle carbonylated protein levels. Interestingly, insulin treatment reduced hyperglycemia and improved systemic and muscular oxidative stress in STZ mice. We demonstrated that increased oxidative stress in muscle of STZ mice is associated with an increase of xanthine oxidase (XO) expression and activity and is mediated by an induction of H2O2 production by both mitochondria and XO. Finally, treatment of STZ mice, as well as high-fat and high-sucrose diet-fed mice, with oxypurinol reduced markers of systemic and muscular oxidative stress and prevented structural and functional mitochondrial alterations, confirming the in vivo relevance of XO in ROS production in diabetic mice. These data indicate that mitochondria and XO are the major sources of hyperglycemia-induced ROS production in skeletal muscle and that the inhibition of XO reduces oxidative stress and improves mitochondrial alterations in diabetic muscle.
Published: 2011
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24. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation

Author: Marie-Caroline Michalski, Cécile Vors, Noël Peretti, Fabienne Laugerette, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Fabienne Laugerette acknowledges grants from Institut Benjamin Delessert and Société Française de Nutrition. Cécile Vors is a recipient of doctoral grand from INRA & CNIEL. Marie-Caroline Michalski acknowledges a grant from ALFEDIAM., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Vericel, Evelyne, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: MESH: Inflammation, Metabolic inflammation, 030309 nutrition & dietetics, Endogeny, MESH: Metabolic Diseases, Biochemistry, Mice, MESH: Endotoxins, MESH: Obesity, MESH: Animals, Intestinal Mucosa, Subclinical infection, MESH: Lipid Metabolism, 0303 health sciences, General Medicine, 3. Good health, Intestines, MESH: Insulin Resistance, MESH: Dietary Fats, lipids (amino acids, peptides, and proteins), medicine.symptom, Digestion, Lipid digestion, MESH: Intestines, medicine.medical_specialty, MESH: Rats, Inflammation, Biology, 03 medical and health sciences, Insulin resistance, Metabolic Diseases, Internal medicine, medicine, Animals, Humans, Obesity, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Metagenome, medicine.disease, Lipid Metabolism, Dietary Fats, Endotoxemia, Rats, Endotoxins, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, MESH: Endotoxemia, Metagenome, Insulin Resistance, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.
Published: 2011
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25. Estimating spatial accessibility to facilities at the regional scale: refining and extending an interaction potential model for proximity services and commuters

Author: Salze, Paul, Banos, Arnaud, Oppert, Jean-Michel, Charreire, Hélène, Casey, Romain, Simon, Chantal, Chaix, Basile, Badariotti, Dominique, Weber, Christiane, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Image, Ville, Environnement [Strasbourg] (LIVE), Université de Strasbourg (UNISTRA), Géographie-cités (GC (UMR_8504)), Université Panthéon-Sorbonne (UP1)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital de l'Hôtel-Dieu, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Nord-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC), Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: spatial accessibility, commuters, interaction potential model, [SHS.GEO]Humanities and Social Sciences/Geography, proximity services
Abstract: Background There is growing interest in the study of the relationships between individual health-related behaviours (e.g. food intake and physical activity) and measurements of spatial accessibility to the associated facilities (e.g. food outlets and sport facilities). The aim of this study is to propose measurements of spatial accessibility to facilities on the regional scale, using aggregated data. We first used a potential accessibility model that partly makes it possible to overcome the limitations of the most frequently used indices such as the count of opportunities within a given neighbourhood. We then propose an extended model in order to take into account both home and work-based accessibility for a commuting population. Results Potential accessibility estimation provides a very different picture of the accessibility levels experienced by the population than the more classical "number of opportunities per census tract" index. The extended model for commuters increases the overall accessibility levels but this increase differs according to the urbanisation level. Strongest increases are observed in some rural municipalities with initial low accessibility levels. Distance to major urban poles seems to play an essential role. Conclusions Accessibility is a multi-dimensional concept that should integrate some aspects of travel behaviour. Our work supports the evidence that the choice of appropriate accessibility indices including both residential and non-residential environmental features is necessary. Such models have potential implications for providing relevant information to policy-makers in the field of public health.
Published: 2011
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26. Metabolic syndrome and diabetes in Humans. Lipid composition and oxidation of low-density lipoproteins in relation with platelet activation

Author: Colas, Romain, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSA de Lyon, Prof. Michel Lagarde et Dr. Catherine Calzad(michel.lagarde @insa-lyon.fr), and Vericel, Evelyne
Subjects: thromboxane A2, syndrome métabolique, blood platelets, peroxydation lipidique, athérothrombose, lipid peroxidation, type-2 diabetes, stress oxydant, p38 MAPK, metabolic syndrome, LDL, acides gras hydroxylés, hydroxylated fatty acids, atherothrombosis, oxidative stress, lipids (amino acids, peptides, and proteins), [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], plaquettes sanguines, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], diabète de type-2
Abstract: Type-2 diabetes and metabolic syndrome are associated with increased oxidative stress and cardiovascular risk. Platelet hyperactivation and dyslipoproteinemia are two major factors favoring atherothrombosis. We have shown that low-density lipoproteins (LDL) from type-2 diabetic patients activate platelets from healthy volunteers. The primary objective of our study was to establish the lipid and lipid peroxide profile of LDL isolated from plasma of volunteers with a metabolic syndrome (SM), of type-1 (DT-1) or type-2 (DT-2) diabetic patients compared to LDL from healthy volunteers (V). The second objective was to explore their role in platelet activation. Only LDL from MS and DT-2 groups have lipid abnormalities (increased triacylglycerols and decreased cholesteryl esters, decreased linoleic acid). LDL from SM, DT-1 and DT-2 groups show oxidative stress as assessed by increased lipid peroxide derivatives (hydroxylated fatty acids, malondialdehyde) and decreased plasmalogens. Compared to platelets incubated with LDL from the V group, platelets incubated with LDL from other groups are activated as shown by the enhancement of the arachidonic acid signalling cascade (p38 MAPK, cytosolic phospholipase A2, thromboxane B2). Thus, in a pre-diabetic state and in type-2 diabetes, LDL undergo lipid and oxidative modifications and activate platelets. Our results show that lipid peroxides in LDL could be the common denominator underlying platelet hyperactivation., Le diabète de type-2 et le syndrome métabolique sont associés à une augmentation du stress oxydant et du risque cardiovasculaire. L'hyperactivation plaquettaire et les dyslipoprotéinémies sont deux causes majeures de l'athérothrombose. Nous avons montré que des lipoprotéines de basse densité (LDL) issues du plasma de diabétiques de type-2 activent les plaquettes sanguines. L'objectif principal de notre étude a été d'établir le profil en lipides et peroxydes lipidiques de LDL provenant de volontaires ayant un syndrome métabolique (SM), un diabète de type-1 (DT-1) ou de type-2 (DT-2), comparativement à celui de volontaires sains (V). Un autre objectif a été de déterminer leur impact sur l'activation plaquettaire. Seules les LDL des groupes SM et DT-2 ont des anomalies lipidiques telles que : augmentation des triacylglycérols, diminution des esters de cholestérol et de l'acide linoléique. Les LDL des groupes SM, DT-1 et DT-2 présentent un stress oxydant, démontré par l'augmentation des produits de peroxydation lipidique comme les acides gras hydroxylés et le dialdéhyde malonique, ainsi que par la diminution des plasmalogènes (sous-classe de phospholipides à éthanolamine). Comparativement aux plaquettes incubées avec les LDL de V, les plaquettes incubées avec les LDL des autres groupes sont activées comme le montre une exacerbation de la cascade de l'acide arachidonique (p38 MAPK, phospholipase A2 cytosolique, thromboxane A2). Ainsi, dans les états pré-diabétique et diabétique de type-2, les LDL subissent des modifications lipidiques et oxydatives, puis activent les plaquettes. Nos résultats suggèrent que les peroxydes lipidiques des LDL induisent l'hyperactivation plaquettaire.
Published: 2010

27. Analysis of lifestyle and metabolic predictors of visceral obesity with Bayesian Networks

Author: Sérgio Rodrigues de Morais, André Tchernof, Alex Aussem, Sophie Rome, Laboratoire d'Informatique pour l'Entreprise et les Systèmes de Production (LIESP), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Endocrinology and Genomics, Laval University [Québec], Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), André Tchernof is the recipient of a Fonds de la recherche en santé du Québec Senior investigator scholarship., Université Laval [Québec] (ULaval), BMC, Ed., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Adipose Tissue, Algorithms, Bayes Theorem, Female, Gene Expression Profiling, Humans, Life Style, Obesity, Abdominal, Inference, 02 engineering and technology, computer.software_genre, Bioinformatics, Biochemistry, Bayes' theorem, Structural Biology, 0202 electrical engineering, electronic engineering, information engineering, lcsh:QH301-705.5, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Applied Mathematics, MESH: Life Style, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, Obesity, Abdominal, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Bio-informatique, lcsh:R858-859.7, 020201 artificial intelligence & image processing, Biological plausibility, MESH: Adipose Tissue, Research Article, MESH: Bayes Theorem, Bayesian probability, Sample (statistics), MESH: Algorithms, Biology, Machine learning, lcsh:Computer applications to medicine. Medical informatics, MESH: Obesity, Abdominal, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Molecular Biology, 030304 developmental biology, MESH: Humans, business.industry, Robustness (evolution), Bayesian network, SDV:BBM:GTP, Constraint (information theory), lcsh:Biology (General), Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, SDV:BIBS, MESH: Female
Abstract: Background The aim of this study was to provide a framework for the analysis of visceral obesity and its determinants in women, where complex inter-relationships are observed among lifestyle, nutritional and metabolic predictors. Thirty-four predictors related to lifestyle, adiposity, body fat distribution, blood lipids and adipocyte sizes have been considered as potential correlates of visceral obesity in women. To properly address the difficulties in managing such interactions given our limited sample of 150 women, bootstrapped Bayesian networks were constructed based on novel constraint-based learning methods that appeared recently in the statistical learning community. Statistical significance of edge strengths was evaluated and the less reliable edges were pruned to increase the network robustness. To allow accessible interpretation and integrate biological knowledge into the final network, several undirected edges were afterwards directed with physiological expertise according to relevant literature. Results Extensive experiments on synthetic data sampled from a known Bayesian network show that the algorithm, called Recursive Hybrid Parents and Children (RHPC), outperforms state-of-the-art algorithms that appeared in the recent literature. Regarding biological plausibility, we found that the inference results obtained with the proposed method were in excellent agreement with biological knowledge. For example, these analyses indicated that visceral adipose tissue accumulation is strongly related to blood lipid alterations independent of overall obesity level. Conclusions Bayesian Networks are a useful tool for investigating and summarizing evidence when complex relationships exist among predictors, in particular, as in the case of multifactorial conditions like visceral obesity, when there is a concurrent incidence for several variables, interacting in a complex manner. The source code and the data sets used for the empirical tests are available at http://www710.univ-lyon1.fr/~aaussem/Software.html.
Published: 2010
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28. Leisure-time physical activity and sedentary behavior clusters and their associations with overweight in middle-aged French adults

Author: Jean-Michel Oppert, Arnaud Banos, Chantal Simon, Mathilde Touvier, Christiane Weber, Emmanuelle Kesse-Guyot, Hélène Charreire, Basile Chaix, Dominique Badariotti, Romain Casey, Paul Salze, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire Image, Ville, Environnement [Strasbourg] (LIVE), Université de Strasbourg (UNISTRA), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut National de la Recherche Agronomique (INRA), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Gerontology, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Health Behavior, multiple correspondence analysis, Medicine (miscellaneous), 030209 endocrinology & metabolism, Physical exercise, Motor Activity, Overweight, Logistic regression, 03 medical and health sciences, Leisure Activities, 0302 clinical medicine, Surveys and Questionnaires, Odds Ratio, medicine, Humans, overweight, 030212 general & internal medicine, Sedentary lifestyle, 2. Zero hunger, Nutrition and Dietetics, middle-aged French adults, Smoking, Odds ratio, leisure-time physical activity clusters, [SHS.GEO]Humanities and Social Sciences/Geography, Middle Aged, Middle age, Cross-Sectional Studies, Female, France, Sedentary Behavior, medicine.symptom, Psychology, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, cluster analysis
Abstract: OBJECTIVE: To identify leisure-time physical activity (LTPA) and sedentary behavior patterns, as well as to investigate their relationships with overweight. DESIGN: Cross-sectional study. SUBJECTS: Men (n=2206) and women (n=2476) aged >45 years, living in France, enrolled in the SU.VI.MAX (Supplémentation en VItamines et Minéraux AntioXydants) study. MEASUREMENTS: LTPA and sedentary behavior were assessed using the Modifiable Activity Questionnaire whereas weight and height were measured from study participants. Clusters were defined, by gender, with multiple correspondence analysis and cluster analysis successively, taking into account the type (walking, gardening, etc.) and duration of each physical activity performed, as well as the time spent watching television (TV) as typical sedentary behavior. Logistic regression models were used to assess associations with overweight. RESULTS: Four physical activity and sedentary behavior clusters were identified among men and three among women. We chose as referent cluster the cluster associating 'walking and gardening-low TV' in men and the cluster associating 'walking and gardening-high TV' in women. Compared with the referent cluster and after adjustment for age, education level, smoking status and place of residence, the likelihood of overweight (defined as body mass index >or=25 kg m(-2)) in women was lower for a 'multiple activity-low TV' cluster (odds ratio (OR)=0.66, 95% confidence interval=0.54-0.81) and for a cluster associating 'endurance physical activity-low TV' (OR=0.42 (0.29-0.60)). Compared with the referent cluster and after adjustment, the likelihood of overweight in men was decreased for the 'endurance physical activity' cluster (OR=0.66, (0.52-0.84)), whereas no significant association was found with the other clusters. CONCLUSIONS: Patterns combining specific types of physical activity and sedentary behavior were identified and differed in their relations to overweight in adults. The identification of global patterns of activity allows us to go beyond a simple decreased activity-increased body weight approach and adds to our understanding of the associations of specific forms and grouping of activity with overweight in adults.
Published: 2010
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29. Increased Lipid Peroxidation in LDL from Type-2 Diabetic Patients

Author: Myriam Moret, Romain A. Colas, Hubert Vidal, Céline Luquain-Costaz, Michel Lagarde, Catherine Calzada, Valérie Pruneta-Deloche, Philippe Moulin, Christine Cugnet-Anceau, Michel Guichardant, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération d'endocrinologie, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and Vericel, Evelyne
Subjects: Male, medicine.medical_specialty, Linoleic acid, 030204 cardiovascular system & hematology, medicine.disease_cause, Biochemistry, fatty acids, Article, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, ultracentrifugation, 0302 clinical medicine, Malondialdehyde, Internal medicine, medicine, Humans, Vitamin E, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, Triglyceride, diabetes, Cholesterol, Organic Chemistry, Cholesterol, LDL, Cell Biology, Middle Aged, peroxidation, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Diabetes Mellitus, Type 2, chemistry, fast-protein liquid chromatography, Low-density lipoprotein, Arachidonic acid, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, plasmalogens, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oxidative stress
Abstract: International audience; Increased oxidative stress is associated with type-2 diabetes and related cardiovascular diseases, but oxidative modification of LDL has been partially characterized. Our aim was to compare the lipid and fatty acid composition as well as the redox status of LDL from diabetic patients and healthy subjects. First, to ensure that isolation of LDL by sequential ultracentrifugation did not result in lipid modifications, lipid composition and peroxide content were determined in LDL isolated either by ultracentrifugation or fast-protein liquid chromatography. Both methods resulted in similar concentrations of lipids, fatty acids, hydroxy-octadecadienoic acid (HODE) and malondialdehyde (MDA). Then, LDLs were isolated by ultracentrifugation from eight type-2 diabetic patients and eight control subjects. Compared to control LDL, diabetic LDL contained decreased cholesteryl esters and increased triglyceride concentrations. Ethanolamine plasmalogens decreased by 49%. Proportions of linoleic acid decreased in all lipid classes, while proportions of arachidonic acid increased in cholesteryl esters. Total HODE concentrations increased by 56%, 12- and 15-hydroxy-eicosatetraenoic acid by 161 and 86%, respectively, and MDA levels increased by twofold. alpha-Tocopherol concentrations, expressed relative to triglycerides, were lower in LDL from patients compared to controls, while gamma-tocopherol did not differ. Overall, LDL from type-2 diabetic patients displayed increased oxidative stress. Determination of hydroxylated fatty acids and ethanolamine plasmalogen depletion could be especially relevant in diabetes.
Published: 2010
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30. Involvement of epigenetic and apoptotic effectors in the hypospermatogenesis induced by endocrine disruptors

Author: leo meunier, Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Université Claude Bernard - Lyon I, Claire Mauduit, Mohamed Benahmed, Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Perturbateurs endocriniens, Apoptose, Infertilité, Reproduction, Épigénétique, Epigenetic, Apoptosis, DNA methyltransferases, Testicule, Hormones, Developmental programming, Cellules germinales, ADN méthyltransférases, MicroRNAs, Testicle, Infertility, Germ cells, Programmation développementale, Endocrine disruptors, [ SDV.SA ] Life Sciences [q-bio]/Agricultural sciences, Cancer
Abstract: During the five past decades, a number of epidemiological studies have indicated a higher incidence of infertility problems, male reproductive tract abnormalities and testicular cancers. Among the different hypotheses proposed, fetal or neonatal exposure to environmental compounds that can interfere with endocrine system, termed endocrine disruptors, may be at the origin of the rising incidence of these diseases. The molecules that are supposed to have long term adverse effects on the male genital tract have estrogenic or antiandrogenic properties. Some authors have suggested that the long term effects of endocrine disruptors could be mediated through epigenetic mechanisms. In this context, we have used two types of experimental models based on developmental exposure to these compounds: one model of neonatal exposure to an estrogen (estradiol benzoate) and another model of fetal exposure to an antiandrogen (flutamide). The two experimental models induce a phenotype of hypospermatogenesis in rodents. In the context of neonatal exposure to estradiol benzoate we show that the hypospermatogenesis observed in adult animals is the consequence of a chronic activation of the apoptotic process of testicular germ cells. This cell death process seem to involve the decrease of the key epigenetic effectors of DNA methylation machinery DNA methyltransferases (DNMT3A, 3B & 1), and of the antiapoptotic protein MCL-1 through post transcriptional mechanisms. In term of functional consequences the decrease of DNMTs proteins leads to increased expression of transposable element LINE-1 and Ibtk gene that are normally controlled by DNA methylation. Upstream DNMTs and MCL-1 decrease may be triggered by the increase of other epigenetic factors, the microRNAs belonging to miR-29 family. Concerning in utero exposure to flutamide, our work indicate that the chronic apoptotic process of germ cells may be linked to long term decrease of the inhibitors of apoptosis cIAP1 & 2, and an increase of proapoptotic factors SMAC/DIABLO. On the other hand, the lack of testicular somatic cell death in this model may be the result of higher expression of inhibitors of apoptosis XIAP and SURVIVIN in these cells. Besides, the apoptotic process observed at the adult age may also involve a precocious alteration of DNMTs expression. In summary, our work provides a mechanistic view to the fetal/neonatal programming of adult germ cell death. Indeed, the increased levels of miR-29s may induce: (1) a decrease in DNMTs expression levels that consequently could alter the methylation pattern of some genes, and (2) a decrease in factors that normally prevent germ cells death such as MCL-1.; Un certain nombre d’études épidémiologiques ont montré au cours des cinquante dernières années une augmentation des infertilités, des malformations de l’appareil reproducteur masculin et des cancers testiculaires. Une des hypothèses est que, l’exposition durant la vie foetale ou néonatale à des composés présents dans l’environnement capables d’interférer avec le système hormonal (perturbateurs endocriniens), serait responsable de l’augmentation de l’incidence de ces pathologies. Les molécules qui sont suspectées d’avoir des effets néfastes à long terme sur le tractus génital mâle possèdent des activités de type estrogénique ou antiandrogénique. Parmi les mécanismes impliqués dans l’effet à long terme, un certain nombre d’auteurs mettent en avant l’intervention de mécanismes de type épigénétiques. Dans ce contexte, nous avons utilisé deux types de modèles expérimentaux reposant sur l’exposition développementale de rats à ces composés : un modèle d’exposition néonatale à un estrogène (estradiol benzoate) et un modèle d’exposition foetale à un antiandrogène (flutamide). Les deux modèles expérimentaux induisent chez le rongeur un phénotype d’hypospermatogenèse. Dans le cas de l’exposition néonatale à l’estradiol benzoate nous montrons que l’hypospermatogenèse observée chez les animaux à l’âge adulte est due à l’activation chronique de l’apoptose des cellules germinales testiculaires. Cette apoptose mettrait en jeu, par un mécanisme post-transcriptionnel, la diminution à long terme de l’expression de protéines clés de la machinerie épigénétique de méthylation de l’ADN, les ADN méthyltransférases (DNMT 3A, 3B et 1), et du facteur antiapoptotique, MCL-1. D’un point de vue fonctionnel, la chute d’expression des DNMTs se traduit notamment par l’augmentation d’expression des éléments transposables LINE-1 et du gène Ibtk normalement contrôlés par méthylation de l’ADN. En amont, la chute d’expression des DNMTs et de MCL-1 serait dépendante de l’augmentation d’expression d’autres effecteurs épigénétiques, les microRNAs de la famille miR-29. Dans le cas de l’exposition in utero au flutamide, notre travail indique que l’apoptose chronique des cellules germinales serait liée à la diminution à long terme de l’expression des inhibiteurs d’apoptose cIAP1 et cIAP2, et une augmentation d’expression de leur inhibiteur SMAC/DIABLO. En revanche, l’absence de mort des cellules somatiques testiculaires (Sertoli et Leydig) dans ce modèle serait due à l’augmentation d’expression spécifiquement dans ces cellules des inhibiteurs d’apoptose XIAP et SURVIVIN. Par ailleurs, le phénotype d’apoptose observé à l’âge adulte impliquerait également une altération précoce de l’expression des DNMTs. En conclusion, nous apportons une réponse mécanistique au phénotype de programmation foetale/néonatale d’apoptose des cellules germinales testiculaires adultes. En effet, l’augmentation des miR-29s provoquerait : (1) une chute d’expression des DNMTs altérant ainsi le profil de méthylation des gènes, et (2) une chute d’expression de facteurs protégeant les cellules germinales contre l’apoptose comme le facteur MCL-1.
Published: 2010

31. Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia

Author: Régis Bonnefoy, Frédéric Costes, Stéphane Baugé, Etienne Lefai, Aurelia Defour, Damien Freyssenet, André Peinnequin, François Bertrand Favier, H. Benoit, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Différenciation Cellulaire et Croissance (DCC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, Sinniger, Valérie, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
Subjects: Male, muscle atrophy, AMPK, MESH: Signal Transduction, Physiology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Anoxia, MESH: Pulmonary Disease, Chronic Obstructive, MESH: Down-Regulation, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, MESH: Animals, Hypoxia, 14-3-3, Mammals, 0303 health sciences, MESH: Muscle, Skeletal, Muscle atrophy, 3. Good health, Muscular Atrophy, medicine.anatomical_structure, medicine.symptom, Signal Transduction, medicine.medical_specialty, MESH: Rats, Down-Regulation, MESH: Atrophy, Biology, MESH: Mammals, 03 medical and health sciences, Atrophy, Downregulation and upregulation, Physiology (medical), Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Rats, Wistar, Muscle, Skeletal, Protein kinase B, PI3K/AKT/mTOR pathway, 030304 developmental biology, Soleus muscle, Sirolimus, MESH: Humans, MESH: Proto-Oncogene Proteins c-akt, MESH: Muscular Atrophy, Skeletal muscle, MESH: Rats, Wistar, Hypoxia (medical), medicine.disease, MESH: Male, Rats, Endocrinology, proteasome, MESH: Sirolimus, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery
Abstract: International audience; Although it is well established that chronic hypoxia leads to an inexorable loss of skeletal muscle mass in healthy subjects, the underlying molecular mechanisms involved in this process are currently unknown. Skeletal muscle atrophy is also an important systemic consequence of chronic obstructive pulmonary disease (COPD), but the role of hypoxemia in this regulation is still debated. Our general aim was to determine the molecular mechanisms involved in the regulation of skeletal muscle mass after exposure to chronic hypoxia and to test the biological relevance of our findings into the clinical context of COPD. Expression of positive and negative regulators of skeletal muscle mass were explored 1) in the soleus muscle of rats exposed to severe hypoxia (6,300 m) for 3 wk and 2) in vastus lateralis muscle of nonhypoxemic and hypoxemic COPD patients. In rodents, we observed a marked inhibition of the mammalian target of rapamycin (mTOR) pathway together with a strong increase in regulated in development and DNA damage response 1 (REDD1) expression and in its association with 14-3-3, a mechanism known to downregulate the mTOR pathway. Importantly, REDD1 overexpression in vivo was sufficient to cause skeletal muscle fiber atrophy in normoxia. Finally, the comparative analysis of skeletal muscle in hypoxemic vs. nonhypoxemic COPD patients confirms that hypoxia causes an inhibition of the mTOR signaling pathway. We thus identify REDD1 as a negative regulator of skeletal muscle mass during chronic hypoxia. Translation of this fundamental knowledge into the clinical investigation of COPD shows the interest to develop therapeutic strategies aimed at inhibiting REDD1.
Published: 2010
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32. Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans

Author: Philippe Valet, Jennifer Jager, Estelle Wanecq, Hubert Vidal, Cyrille Debard, Frédéric Bost, Camille Attané, Cédric Dray, Isabelle Castan-Laurell, Emmanuel Disse, Charlotte Guigné, Danièle Daviaud, Jean-François Tanti, Pascal G.P. Martin, Martine Laville, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique (INRA), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Leptin, Male, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Messenger, Adipose tissue, Inbred C57BL, Receptors, G-Protein-Coupled, Mice, 0302 clinical medicine, Receptors, Insulin, Glucose homeostasis, Apelin Receptors, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Skeletal, Middle Aged, Glucose clamp technique, Apelin, medicine.anatomical_structure, Adipose Tissue, Intercellular Signaling Peptides and Proteins, Muscle, Female, Type 2, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Biology, G-Protein-Coupled, 03 medical and health sciences, Insulin resistance, Adipokines, Physiology (medical), Internal medicine, Diabetes Mellitus, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Muscle, Skeletal, 030304 developmental biology, Apelin receptor, Skeletal muscle, medicine.disease, Mice, Inbred C57BL, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, Carrier Proteins, Glucose Clamp Technique, Insulin Resistance, RNA
Abstract: International audience; Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity. Apelin was recently identified as a new player in the control of glucose homeostasis. However, the regulation of apelin and APJ (apelin receptor) expression in skeletal muscle in relation to insulin resistance or type 2 diabetes is not known. Thus we studied apelin and APJ expression in AT and muscle in different mice models of obesity and in type 2 diabetic patients. In insulin-resistant high-fat (HF)-fed mice, apelin and APJ expression were increased in AT compared with control. This was not the case in AT of highly insulin-resistant db/db mice. In skeletal muscle, apelin expression was similar in control and HF-fed mice and decreased in db/db mice. APJ expression was decreased in both HF-fed and db/db mice. Control subjects and type 2 diabetic patients were subjected to a hyperinsulinemic-euglycemic clamp, and tissues biopsies were obtained before and at the end of the clamp. There was no significant difference in basal apelin and APJ expression in AT and muscle between control and diabetic patients. However, apelin plasma levels were significantly increased in diabetic patients. During the clamp, hyperinsulinemia increased apelin and APJ expression in AT of control but not in diabetic subjects. In muscle, only APJ mRNA levels were increased in control but also in diabetic patients. Taken together, these data show that apelin and APJ expression in mice and humans is regulated in a tissue-dependent manner and according to the severity of insulin resistance.
Published: 2010
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33. Quantitative structure-activity relationship for 4-hydroxy-2-alkenal induced cytotoxicity in L6 muscle cells

Author: Roxane E. Vella, Marine L. Croze, Michel Lagarde, Laurent Soulère, Bertrand R. Caré, Christophe O. Soulage, Hédi Soula, Alain Doutheau, Nicolas J. Pillon, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Organique (LCO), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), INSERM, INSA-Lyon, French 'Ministere de l'Education Nationale, de la Recherche et de la Technologie', Region Rhone-Alpes, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)
Subjects: END-PRODUCTS, Stereochemistry, DNA damage, Protein Carbonylation, Lipid peroxidation, INCREASED OXIDATIVE STRESS, Quantitative Structure-Activity Relationship, Apoptosis, Alkenes, Toxicology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, 4-Hydroxy-2-hexenal, QSTR, 0302 clinical medicine, medicine, Animals, OXIDIZED PHOSPHOLIPIDS, Viability assay, Cells, Cultured, 030304 developmental biology, POLYUNSATURATED FATTY-ACIDS, 0303 health sciences, Aldehydes, INSULIN-RESISTANCE, Nucleophilic addition, RAT HEPATOCYTES, L-Lactate Dehydrogenase, Caspase 3, Muscles, Acetal, EPITHELIAL-CELLS, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], LIPID-PEROXIDATION PRODUCT, Rats, chemistry, Biochemistry, HYDROXY-ALKENALS, DNA-DAMAGE, Covalent bond, Oxidative stress, 4-Hydroxy-2-nonenal, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery
Abstract: International audience; Lipid peroxidation is one of the most important sources of endogenous toxic metabolites. 4-Hydroxy-2-nonenal (HNE) and 4-hydroxy-2-hexenal (HHE) are produced in several oxidative stress associated diseases from peroxidation of n-6 and n-3 polyunsaturated fatty acids, respectively. Both are able to form covalent adducts with many biomolecules. Particularly, proteins adduction can induce structural and conformational changes and impair biological function, which may be involved in the toxicity of hydroxy-alkenals. The aim of this study was to compare the effect of 4-hydroxy-2-alkenals to several chemically related derivatives in order to clarify the physico-chemical requirement of their toxicity. L6 muscle cells were treated with HHE, HNE and parent derivatives (acetal derivative, trans-alkenals and alkanals). Viability and necrosis were estimated using MTT, LDH and caspase-3 tests. LogLC50 (Lethal Concentration 50) was then tested for correlation with adducts formation (estimated using dinitrophenylhydrazine) and several molecular descriptors in order to establish quantitative structure-toxicity relationship (QSTR) models. The rank of derivatives toxicity, based on LC50 was: hydroxy-alkenals>acetal derivatives approximately 2-alkenals>alkanals and a high correlation was found between logLC50 and protein carbonylation. Moreover, logLC50 was correlated to the electrophilic descriptor LUMO (lowest unoccupied molecular orbital) as well as with electronegativity-related molecular descriptors such as number of oxygen atoms, partial negative surface area (PNSA3) and partial positive surface area (PPSA3). Together, these results point out the important role of the electrophilic structure and adduct formation in hydroxy-alkenals toxicity. Our present study demonstrates that 4-hydroxy-2-alkenals dramatic effects on cell viability are due to covalent adducts formation, particularly Michael adducts. This capacity is related to the electrophilic structure and reactive CC double bond, making it highly accessible for nucleophilic addition. The present study suggests that nucleophilic scavengers might protect cells against electrophile compounds and might be of possible therapeutic value in oxidative stress associated diseases.
Published: 2010
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34. Cirsimarin, a potent antilipogenic flavonoid, decreases fat deposition in mice intra-abdominal adipose tissue

Author: Lucie Grand, Alain Géloën, Emilie Kalbacher, Stéphane Chambert, Hédi Soula, Nicolas J. Pillon, Bader Zarrouki, G Nia N'Jomen, Christophe O. Soulage, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de Chimie Organique (LCO), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), French 'Ministere de l'Education Nationale, de la Recherche et de la Technologie', INSA-Lyon [BQR 2009], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Adipose tissue, Cell Count, White adipose tissue, REDUCES FOOD-INTAKE, Fat pad, Mice, chemistry.chemical_compound, 0302 clinical medicine, Adipocyte, Adipocytes, Glycosides, DEPENDENT PROTEIN-KINASE, GENE-EXPRESSION, 0303 health sciences, Nutrition and Dietetics, MICROTEA-DEBILIS, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, 030220 oncology & carcinogenesis, Lipogenesis, Injections, Intraperitoneal, medicine.medical_specialty, Ratón, OBESE MICE, BODY-FAT, Intra-Abdominal Fat, 03 medical and health sciences, white adipose tissue, cellularity, In vivo, Internal medicine, medicine, Animals, Lipolysis, flavonoid, lipogenesis, Cell Size, 030304 developmental biology, RECEPTOR, Body Weight, cirsimarin, Flavones, Rats, ISOLATED RAT ADIPOCYTES, ACSYNTHASE INHIBITOR, Endocrinology, chemistry, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], GREEN TEA
Abstract: International audience; OBJECTIVE: We previously reported that the flavonoid cirsimarin exerts in vitro a strong lipolytic activity on isolated adipocytes. This study was therefore designed to evaluate in vivo the effects of cirsimarin on white adipose tissue (WAT) accretion in mice. METHODS: Male CD1 mice were injected daily with either vehicle (intraperitoneal (i.p.)) or cirsimarin (25 or 50 mg kg(-1) per day, i.p.) for 18 days. Mice were killed and fat pads weighted. Epididymal fat pads were used for cellularity measurement. Effects of cirsimarin treatment on lipolysis and lipogenesis in WAT were assessed. RESULTS: Mice treated with 25 or 50 mg kg(-1) per day cirsimarin showed a decrease in retroperitoneal (-29 and -37% respectively, P
Published: 2010
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35. A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation

Author: Lecomte, Virginie, Meugnier, Emmanuelle, Euthine, Vanessa, Durand, Christine, Freyssenet, Damien, Nemoz, Georges, Rome, Sophie, Vidal, Hubert, Lefai, Etienne, Service de Diabétologie et Nutrition, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Physiologie et Physiopathologie de l'Exercice et Handicap, Université Jean Monnet [Saint-Étienne] (UJM), This work was supported by the Programme National de Recherche sur le Diabète (grant to E. Lefai). V. Lecomte is supported by a doctoral fellowship from the Fondation pour la Recherche Médicale., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: MESH: Cell Differentiation, MESH: Myoblasts, Skeletal, MESH: Muscle, Skeletal, MESH: Humans, MESH: Muscle Fibers, Skeletal, MESH: Mice, Transgenic, MESH: Muscular Atrophy, MESH: Mice, Inbred BALB C, MESH: Down-Regulation, MESH: Male, MESH: Recombinant Proteins, MESH: Sterol Regulatory Element Binding Protein 1, MESH: Repressor Proteins, MESH: Basic Helix-Loop-Helix Transcription Factors, MESH: Homeodomain Proteins, MESH: Oligonucleotide Array Sequence Analysis, MESH: Promoter Regions, Genetic, MESH: Muscle Development, lipids (amino acids, peptides, and proteins), MESH: Animals, MESH: Mice, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Cells, Cultured
Abstract: International audience; The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.
Published: 2010
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36. Phospholipides dans le fluide synovial - influence sur le fonctionnement tribologique des articulations synoviales pathologiques

Author: Corneci, Magdalena, Trunfio-Sfarghiu, Ana-Maria, Dekkiche, Fairouz, Berthier, Yves, Meurisse, Marie-Hélène, Rieu, Jean-Paul, Lagarde, Michel, Guichardant, Michel, Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Faculté de Mécanique, 'Gheorghe Asachi' Technical University of Iasi (TUIASI), Tribologie et Mécanique des Interfaces (TMI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Laboratoire de Physique de la Matière Condensée et Nanostructures (LPMCN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département de Chimie, Université Mentouri Constantine [Algérie] (UMC), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Covalab-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: lipidomic analysis, biotribology, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], synovial joints, phospholipids, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: International audience; Des études récentes ont montré le rôle des assemblages lipidiques associées à la structure discontinue du fluide synovial dans les performances du fonctionnement tribologique d'une articulation saine. Dans le cas des pathologies articulaire, ce fonctionnement est modifié. Ce travail cherche ainsi à identifier l'influence de la variation en composition lipidique des fluides synoviaux pathologiques sur le fonctionnement tribologique des articulations synoviales atteintes de différentes pathologies (arthrite, arthrose)
Published: 2010

37. Vocal communication at the nest between mates in wild zebra finches: a private vocal duet?

Author: Nicolas Mathevon, Simon C. Griffith, Julie E. Elie, Mylene M. Mariette, Hédi Soula, Clémentine Vignal, Ecologie et Neuro-Ethologie Sensorielles (ENES), Université Jean Monnet [Saint-Étienne] (UJM), Macquarie University, Equipe 7 : Neuro-Ethologie Sensorielle, Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Ecologie et Neuro-Ethologie Sensorielle (ENES), Université Jean Monnet - Saint-Étienne (UJM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, French Agence Nationale de la Recherche (ANR, project ‘Birds’ voices’, ANR-06-BLAN-0293-01), Australian Research Council grant (DP0881019), oung Investigator Sabbatical of the Universite de Saint-Etienne, Institut Universitaire de France, French Ministry of Research, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Université Lumière - Lyon 2 (UL2)
Subjects: 0106 biological sciences, Vocal communication, vocal duet, social monogamy, 010603 evolutionary biology, 01 natural sciences, reproduction, 03 medical and health sciences, Nest, Animal communication, private communication, Taeniopygia guttata, Zebra finch, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Communication, biology, acoustic communication, business.industry, zebra finch, biology.organism_classification, Mating system, songbird, Pair bond, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Songbird, Animal Science and Zoology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, pair bond, Taeniopygia
Abstract: International audience; Bird vocal duets are joint displays where two individuals, generally a mated pair, produce temporally coordinated vocalizations. Duets may contribute to pair bond maintenance, mate guarding or collaborative defence of resources. The degree of coordination between mates and the variety of vocalizations, however, vary considerably. Although only 3-4.3% of bird species have been reported to duet, this may be because studies have generally focused on conspicuous duets, and more private forms of duet might have been overlooked. We investigated private vocal communication between mates in wild zebra finches, Taeniopygia guttata, a gregarious Australian songbird that forms life-long pair bonds. The partners are inseparable unless nest building, incubating or brooding. Using microphones inside nestboxes, we monitored interactive communication between partners at the nest and its variation during different stages of breeding. After periods of separation, partners performed coordinated mutual vocal displays involving specific soft vocal elements that fulfilled all the criteria used to define duets. In addition, using playback experiments, we obtained preliminary results suggesting that these soft calls could allow mate recognition. Thus, we propose that mutual displays at the nest in zebra finches represent private vocal duets and may function to mediate pair bond maintenance.
Published: 2010
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38. Pdro, a protein associated with late endosomes and lysosomes and implicated in cellular cholesterol homeostasis

Author: Mouhannad Malek, Didier Grunwald, Céline Luquain, Serge Manié, Sabine Brugière, Virginie Pétrilli, Jérôme Garin, Anne-Laure Huber, Daniel Regnier, Etienne Lefai, Patricia Guillaumot, Génétique moléculaire, signalisation et cancer (GMSC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire de chimie des protéines, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANTE-INSERM U836, équipe 4, Muscles et pathologies, Transduction du signal : signalisation calcium, phosphorylation et inflammation, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by institutional grants from CNRS and additional support from Association pour la Recherche contre le Cancer (ARC: SM 3811 and 4915), Fondation De France (FDF: 2002 010 893) and Ligue Nationale Contre le Cancer Comite du Rhone. CL was supported by fellowships from FDF., Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Manié, Serge N., and Roux-Buisson, Nathalie
Subjects: Small interfering RNA, MESH: Lipoproteins, LDL, lcsh:Medicine, Fluorescent Antibody Technique, MESH: Flow Cytometry, MESH: Amino Acid Sequence, MESH: Base Sequence, Cell membrane, chemistry.chemical_compound, 0302 clinical medicine, MESH: Cholesterol, Tandem Mass Spectrometry, MESH: Reverse Transcriptase Polymerase Chain Reaction, Homeostasis, lcsh:Science, Peptide sequence, MESH: Fluorescent Antibody Technique, Late endosome, 0303 health sciences, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Intracellular Signaling Peptides and Proteins, cholestérol, Flow Cytometry, Cell biology, Lipoproteins, LDL, Cholesterol, medicine.anatomical_structure, Biochemistry, protéine, MESH: Homeostasis, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, lysosome, lipids (amino acids, peptides, and proteins), Research Article, MESH: DNA Primers, Endosome, MESH: Biological Transport, Molecular Sequence Data, MESH: Carrier Proteins, Endosomes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Cell Biology/Membranes and Sorting, medicine, Humans, Amino Acid Sequence, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, endosome, Cell Biology/Chemical Biology of the Cell, Actin, homéostasie, DNA Primers, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, lcsh:R, MESH: Tandem Mass Spectrometry, Biological Transport, Cell Biology, MESH: Gene Knockdown Techniques, chemistry, MESH: Endosomes, lcsh:Q, Carrier Proteins, Lysosomes, MESH: Lysosomes
Abstract: International audience; BACKGROUND: Cellular cholesterol is a vital component of the cell membrane. Its concentration is tightly controlled by mechanisms that remain only partially characterized. In this study, we describe a late endosome/lysosomes-associated protein whose expression level affects cellular free cholesterol content. METHODOLOGY/PRINCIPAL FINDINGS: Using a restricted proteomic analysis of detergent-resistant membranes (DRMs), we have identified a protein encoded by gene C11orf59. It is mainly localized to late endosome/lysosome (LE/LY) compartment through N-terminal myristoylation and palmitoylation. We named it Pdro for protein associated with DRMs and endosomes. Very recently, three studies have reported on the same protein under two other names: the human p27RF-Rho that regulates RhoA activation and actin dynamics, and its rodent orthologue p18 that controls both LE/LY dynamics through the MERK-ERK pathway and the lysosomal activation of mammalian target of rapamycin complex 1 by amino acids. We found that, consistent with the presence of sterol-responsive element consensus sequences in the promoter region of C11orf59, Pdro mRNA and protein expression levels are regulated positively by cellular cholesterol depletion and negatively by cellular cholesterol loading. Conversely, Pdro is involved in the regulation of cholesterol homeostasis, since its depletion by siRNA increases cellular free cholesterol content that is accompanied by an increased cholesterol efflux from cells. On the other hand, cells stably overexpressing Pdro display reduced cellular free cholesterol content. Pdro depletion-mediated excess cholesterol results, at least in part, from a stimulated low-density lipoprotein (LDL) uptake and an increased cholesterol egress from LE/LY. CONCLUSIONS/SIGNIFICANCE: LDL-derived cholesterol release involves LE/LY motility that is linked to actin dynamics. Because Pdro regulates these two processes, we propose that modulation of Pdro expression in response to sterol levels regulates LDL-derived cholesterol through both LDL uptake and LE/LY dynamics, to ultimately control free cholesterol homeostasis.
Published: 2010
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39. Claudin 11 deficiency in mice results in loss of the Sertoli cell epithelial phenotype in the testis

Author: Mazaud-Guittot, Séverine, Meugnier, Emmanuelle, Pesenti, Sandra, Wu, Xin, Vidal, Hubert, Gow, Alexander, Le Magueresse-Battistoni, Brigitte, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Center For Molecular Medicine and Genetics, Wayne State University [Detroit], Supported by the Institut National de la Sante ́ et de la Recherche Me ́ dicale (INSERM), Institut National et de la Recherche Agronomique (INRA), University Lyon I, and partly from grants to B.L.M.B. by ANR (ANR-06-PNRA-006) and AFSSET (EST-2006/1/33), and grants by the National Institute on Deafness and Other Communication Disorders, National Institutes of Health (DC006262) to A.G, Vericel, Evelyne, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: endocrine system, MESH: Cell Transdifferentiation, MESH: Apoptosis, MESH: Claudins, MESH: Phenotype, MESH: Actins, MESH: Male, MESH: Tight Junctions, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Gene Expression Profiling, MESH: Sertoli Cells, MESH: Mice, Inbred C57BL, MESH: Oligonucleotide Array Sequence Analysis, MESH: Blood-Testis Barrier, MESH: Cell Division, MESH: Animals, MESH: Nerve Tissue Proteins, MESH: Cell Polarity, MESH: Mice, MESH: Spermatogenesis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Tissue integrity relies on barriers formed between epithelial cells. In the testis, the barrier is formed at the initiation of puberty by a tight junction complex between adjacent Sertoli cells, thereby defining an adluminal compartment where meiosis and spermiogenesis occur. Claudin 11 is an obligatory protein for tight junction formation and barrier integrity in the testis. It is expressed by Sertoli cells, and spermatogenesis does not proceed beyond meiosis in its absence, resulting in male sterility. Sertoli cell maturation--arrest of proliferation and expression of proteins to support germ cell development--parallels tight junction assembly; however, the pathophysiology underlying the loss of tight junctions in the mature testis remains largely undefined. Here, using immunohistochemistry and microarrays we demonstrate that adult Cldn11(-/-) mouse Sertoli cells can proliferate while maintaining expression of mature markers. Sertoli cells detach from the basement membrane, acquire a fibroblast cell shape, are eliminated through the lumen together with apoptotic germ cells, and are found in epididymis. These changes are associated with tight junction regulation as well as actin-related and cell cycle gene expression. Thus, Cldn11(-/-) Sertoli cells exhibit a unique phenotype whereby loss of tight junction integrity results in loss of the epithelial phenotype.
Published: 2010
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40. Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers

Author: Alain Lachaux, Emile Levy, Lise Bouthillier, Agnès Sassolas, Sylvie Labarge, Mathilde Charcosset, Philippe Moulin, Noël Peretti, Colette Deslandres, Justine Castagnetti, Claude C. Roy, Laurence Pugnet-Chardon, Department of Nutrition, CHU Sainte-Justine Research Center, Service de nutrition-hépato gastroentérologie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UF Dyslipidemia Laboratory, Hospices Civils de Lyon (HCL)-Hôpital Neurologique et Cardilogique, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Pediatrics, This study was supported by the Canadian Institutes of Health Research (EL, MOP 10584) and the J.A. de Sève Research Chair in Nutrition (EL). Dr. Peretti's fellowship was supported by a Lavoisier grant from the French Ministry of Foreign Affairs., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal]-Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Pediatrics, MESH: Vitamin E Deficiency, Lipid Metabolism Disorders, lcsh:Medicine, Review, [SDV.GEN] Life Sciences [q-bio]/Genetics, Cohort Studies, MESH: Lipid Metabolism Disorders, 0302 clinical medicine, MESH: Child, Chylomicrons, Genetics(clinical), Pharmacology (medical), Vitamin E Deficiency, Child, MESH: Cohort Studies, Genetics (clinical), Growth Disorders, 2. Zero hunger, Medicine(all), 0303 health sciences, biology, Anthropometry, Fatty Acids, General Medicine, SAR1B, SDV:GEN, MESH: Growth Disorders, MESH: Infant, 3. Good health, MESH: Chylomicrons, MESH: Fatty Acids, MESH: Malabsorption Syndromes, MESH: Diarrhea, Child, Preschool, Failure to thrive, Female, Vitamin E deficiency, medicine.symptom, MESH: Malnutrition, Chylomicron retention disease, Adult, Diarrhea, medicine.medical_specialty, MESH: Mutation, MESH: Monomeric GTP-Binding Proteins, MESH: Nervous System Diseases, 03 medical and health sciences, Malabsorption Syndromes, MESH: Anthropometry, Internal medicine, medicine, Humans, Preschool, 030304 developmental biology, Monomeric GTP-Binding Proteins, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, business.industry, Infant, Malnutrition, Mutation, Nervous System Diseases, lcsh:R, MESH: Child, Preschool, Abetalipoproteinemia, MESH: Adult, medicine.disease, MESH: Male, Hypocholesterolemia, Endocrinology, biology.protein, Hypobetalipoproteinemia, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined. The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience. The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation. Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications.
Published: 2010
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41. A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation

Author: Lecomte, Virginie, Meugnier, Emmanuelle, Euthine, Vanessa, Durand, Christine, Freyssenet, Damien, Nemoz, Georges, Rome, Sophie, Vidal, Hubert, Lefai, Etienne, Vericel, Evelyne, Service de Diabétologie et Nutrition, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Physiologie et Physiopathologie de l'Exercice et Handicap, Université Jean Monnet - Saint-Étienne (UJM), and This work was supported by the Programme National de Recherche sur le Diabète (grant to E. Lefai). V. Lecomte is supported by a doctoral fellowship from the Fondation pour la Recherche Médicale.
Subjects: MESH: Cell Differentiation, MESH: Myoblasts, Skeletal, MESH: Muscle, Skeletal, MESH: Humans, MESH: Muscle Fibers, Skeletal, MESH: Mice, Transgenic, MESH: Muscular Atrophy, MESH: Mice, Inbred BALB C, MESH: Down-Regulation, MESH: Male, MESH: Recombinant Proteins, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Sterol Regulatory Element Binding Protein 1, MESH: Repressor Proteins, MESH: Basic Helix-Loop-Helix Transcription Factors, MESH: Homeodomain Proteins, MESH: Oligonucleotide Array Sequence Analysis, MESH: Promoter Regions, Genetic, MESH: Muscle Development, lipids (amino acids, peptides, and proteins), MESH: Animals, MESH: Mice, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Cells, Cultured
Abstract: International audience; The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.
Published: 2010
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42. The effects of an in utero exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin on male reproductive function: identification of Ccl5 as a potential marker

Author: Sandra Pesenti, P. Leduque, Diane Rebourcet, B. Le Magueresse-Battistoni, F. Odet, Emmanuel Combe, A. Vérot, Solange Magre, H. Déchaud, Emmanuelle Meugnier, Vericel, Evelyne, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hormones steroïdes et protéines de liaison, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Inserm, INRA, University of Lyon 1, and specific grants to BLMB from AFSSET (EST- 2006 ⁄ 1 ⁄ 33) and ANR (ANR-06-PNRA-006-01)., Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Polychlorinated Dibenzodioxins, Endocrinology, Diabetes and Metabolism, MESH: Rats, Sprague-Dawley, Testicle, MESH: Reproduction, MESH: Down-Regulation, Rats, Sprague-Dawley, Ccl5/Rantes, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, heterocyclic compounds, MESH: Animals, MESH: Maternal Exposure, Chemokine CCL5, transcriptomic analysis, Testosterone, reproductive and urinary physiology, 0303 health sciences, MESH: Sperm Count, Sperm Count, Original Articles, Reviews and Commentary, MESH: Testis, Reproduction, in utero exposure, MESH: Cytochrome P-450 CYP1A1, medicine.anatomical_structure, Liver, Maternal Exposure, In utero, Prenatal Exposure Delayed Effects, Female, medicine.medical_specialty, endocrine system, MESH: Rats, Offspring, Urology, Down-Regulation, testis, Biology, CCL5, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, Internal medicine, Cytochrome P-450 CYP1A1, medicine, Animals, Endocrine system, MESH: Chemokine CCL5, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 030304 developmental biology, Sperm, MESH: Male, Rats, MESH: Tetrachlorodibenzodioxin, stomatognathic diseases, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Reproductive Medicine, Spermatogenesis, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, MESH: Liver
Abstract: International audience; 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds are widely encountered toxic substances suspected of interfering with the endocrine systems of humans and wildlife, and of contributing to the loss of fertility. In this study, we determined the changes in testicular gene expression caused by in utero exposure to TCDD along with the intra-testicular testosterone levels, epididymal sperm reserves, daily sperm production (DSP) and testis histology. To this purpose, female pregnant Sprague-Dawley rats orally received TCDD (10, 100 or 200 ng/kg body weight) or vehicle at embryonic day 15, and the offspring was killed throughout development. Hepatic Cyp1a1 gene expression was measured in the offspring to confirm the exposure to TCDD. The gross histology of the testes and intra-testicular testosterone levels were normal among the studied groups. Sperm reserves were altered in 67-day-old rats of the TCDD-200 group, but not in 145-day-old animals or in the other TCDD-exposed groups. Nonetheless, fertility was not altered in males of the TCDD-200 group, and the F2 males generated had normal sperm reserves and DSP. Microarray analysis permitted the identification of eight differentially expressed genes in the 4-week-old testes of the TCDD-200 compared with that of the control group (cut-off value +/- 1.40), including the down-regulated chemokine Ccl5/Rantes. Inhibition of Ccl5/Rantes gene expression was observed throughout development in the TCDD-200 group, and at 67 and 145 days in the TCDD-100 group (animals of younger ages were not examined). Ccl5/Rantes gene expression was mostly confined in Leydig cells. F2 males generated from males of the TCDD-200 group had normal levels of Ccl5/Rantes in testis and Cyp1a1 in liver, which might indicate that Ccl5/Rantes is a marker of TCDD exposure in testis such as Cyp1a1 in liver. In conclusion, we demonstrated a decrease in Ccl5/Rantes RNA levels and a transitory decline in sperm reserves in the testes of rats of TCDD-dosed dams.
Published: 2010
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43. Electronic states of MgO: Spectroscopy, predissociation, and cold atomic Mg and O production

Author: A. Ben Houria, Nejm-Eddine Jaidane, Majdi Hochlaf, A. Maatouk, O. Yazidi, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.PHYS.PHYS-CLASS-PH]Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], Valence (chemistry), 010304 chemical physics, Chemistry, Transition dipole moment, General Physics and Astronomy, Rotational–vibrational spectroscopy, Configuration interaction, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, symbols.namesake, 0103 physical sciences, symbols, Physics::Atomic and Molecular Clusters, Fermi's golden rule, Fermi resonance, Physical and Theoretical Chemistry, Atomic physics, Spectroscopy, Basis set
Abstract: International audience; We used multiconfigurational methods and a large basis set to compute the potential energy curves of the valence and valence-Rydberg electronic states of MgO molecule. New bound electronic states are found. Using these highly correlated wave functions, we evaluated their mutual spin-orbit couplings and transition moment integrals. For the bound electronic states of MgO, we deduced an accurate set of spectroscopic constants that agree remarkably well with experimental results. Moreover, our potentials, transition moments, and spin-orbit coupling evolutions are incorporated into Fermi golden rule calculations to deduce the radiative lifetimes of MgO(B (1)Sigma(+)) rovibrational levels and the natural lifetimes of MgO(A (1)Pi) vibrational levels, where a good agreement is found with experimental values. Finally, we suggest new routes for the production of cold Mg and O atoms and cold MgO molecules. (C) 2010 American Institute of Physics. [doi:10.1063/1.3498900]
Published: 2010
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44. Theoretical spectroscopy and metastability of BeS and its cation

Author: S. Lahmar, T. Larbi, F. Khadri, Majdi Hochlaf, Hassen Ghalila, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 010304 chemical physics, Chemistry, General Physics and Astronomy, 02 engineering and technology, Electronic structure, 021001 nanoscience & nanotechnology, 01 natural sciences, Diatomic molecule, Ab initio quantum chemistry methods, Metastability, Ionization, 0103 physical sciences, Bound state, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, Ionization energy, Atomic physics, 0210 nano-technology, Spectroscopy
Abstract: International audience; Multiconfiguration self-consistent field and multiconfiguration reference interaction including the Davidson's correction techniques were employed to calculate the potential energy curves (PECs) of the BeS/BeS+ electronic states correlating to the 4/5 lowest dissociation limits. After nuclear motion treatment, we deduced reliable spectroscopic data for the neutral and cationic bound states. For BeS, the transition moments and spin-orbit couplings were also evaluated and used later with the PECs to deduce the rovibronic transition probabilities and the radiative lifetimes in the low-lying states, and to investigate the unimolecular decomposition processes of BeS (X(1)Sigma(+), A(1)Pi, (3)Sigma(+) and B(1)Sigma(+)) leading to Be((1)S(g)) + S((3)P(g)). The prominent mechanism is a spin-orbit induced predissociation via the repulsive BeS(1(3)Sigma) state. Finally, we give the single ionization spectrum of BeS (X(1)Sigma(+)) populating the BeS(+) (X(2)Pi, 1(2)Sigma, 1(2)Sigma(+), 1(2)Sigma(+), 2(2)Sigma(+), 2(2)Pi and 3(2)Pi) electronic states. The adiabatic ionisation energy of BeS is estimated to be similar to 9.15 eV. (C) 2010 Published by Elsevier B. V.
Published: 2010
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45. Modulation de la phase postprandiale du glucose

Author: Nazare, Julie-Anne, Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard - Lyon I, Martine Laville, Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA )
Subjects: Isotopes stables, Lipolyse, Lipolysis, Glucose bioavailability, Fibres, Métabolisme postprandial du glucose, Biodisponibilité du glucose, Ghrelin, Ghréline, Index glycémique, Insuline, Postprandial glucose metabolism, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Glycemic index, Insulin, Fiber, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Stable isotopes
Abstract: The reduction of the postprandial glycemic excursions has been proposed as to limit risk of type 2 diabetes. There has been growing interest in the development of dietary ingredients that could potentially modulate carbohydrates bioavailability and thus their impact on postprandial glycemia. The aim of this thesis was to investigate the effects of the the modulation of glucose bioavailability by different ingredients on 2-hour glycemic response but also on glucose kinetics (total, exogenous and endogenous – stable isotopes) and on other daylong metabolic parameters. In the first study (β-glucanes), we showed that the addition of β-glucan fiber to a carbohydrate meal in healthy overweight subjects reduced the appearance of glucose in plasma. As a consequence, insulin response was also prolonged and induced a prolonged inhibition on lipolysis and endogenous glucose production. In the second study (eurostarch), the reduction in glucose availability (slowly available glucose, low GI) at breakfast decreased plasma exogenous glucose appearance and tended to improve glucose control at the subsequent lunch. But we did not observe the improvement of such metabolic effects in the long-term (5 weeks). In the last study, we showed that the addition of a resistant dextrin, NUTRIOSE®10, decreased postprandial glycemic and insulinemic response as well as daylong satiety-related ghrelin profile, compared to maltodextrin. In parallel, the prolonged fermentation and oxidation pattern of NUTRIOSE®10 up to 10 hours after ingestion at breakfast could induced an extended energy release with NUTRIOSE®10 in the late postprandial phase. In conclusion, the follow-up of metabolic parameters beyond 2 hours after the meal have highlighted the longer-term metabolic effects of the modulation of glucose appearance in plasma (delay, extension, reduction) on glucose kinetics, insulin response, lipolysis and nutrients oxidation; La réduction des excursions glycémiques postprandiales a été proposée comme un moyen pour limiter le risque de développement du diabète de type 2. L’intérêt s’est donc porté sur les outils nutritionnels susceptibles de moduler la biodisponibilité des glucides et ainsi leur impact sur la glycémie postprandiale. Les travaux réalisés au cours de cette thèse avaient pour but d’étudier les effets de différents ingrédients modifiant la biodisponibilité du glucose, non seulement sur la glycémie postprandiale à court terme (2 heures) mais aussi sur les cinétiques du débit d’apparition et de disparition de glucose (total, exogène et endogène - isotopes stables) et les autres paramètres métaboliques de la phase postprandiale au cours de la journée. Dans la première étude (β-glucanes), nous avons montré que l’addition de fibres β-glucanes à un repas glucidique chez des sujets sains en surpoids ralentit l’absorption du glucose dans le plasma. Ceci a prolongé la réponse insulinique et par conséquent l’inhibition de la lipolyse et de la production endogène de glucose. Dans la deuxième étude (Eurostarch), nous avons montré que la diminution de la biodisponibilité du glucose au petit-déjeuner (amidon lentement digestible, index glycémique bas) diminue l’apparition du glucose exogène dans le plasma et pourrait avoir un effet second-repas chez des sujets sains en surpoids. Mais nous n’avons pas mis en évidence d’amélioration de ces effets métaboliques à plus long terme (5 semaines). Dans la troisième étude présentée (Nutriose), nous avons montré que l’addition de dextrine résistante NUTRIOSE®10 (fermentescible) au petit-déjeuner chez des sujets sains, diminue les réponses glycémiques, insuliniques postprandiales et le profil de ghréline au cours de la journée (en comparaison à une maltodextrine). En parallèle, la prolongation observée de la fermentation et l’oxydation du NUTRIOSE®10 pourraient fournir de l’énergie en phase postprandiale tardive. En conclusion, l’analyse des paramètres métaboliques au-delà de 2 heures après le repas, a permis de mettre en évidence les effets métaboliques à plus long terme de la modulation de l’apparition du glucose dans le plasma (ralentissement, prolongation, réduction) sur les cinétiques du glucose, la réponse insulinique, la lipolyse et l’oxydation des substrats
Published: 2009

46. The microRNA Signature in Response to Insulin Reveals Its Implication in the Transcriptional Action of Insulin in Human Skeletal Muscle and the Role of a Sterol Regulatory Element-Binding Protein-1c/Myocyte Enhancer Factor 2C Pathway

Author: Etienne Lefai, Hubert Vidal, Sophie Rome, Rémi Rabasa-Lhoret, Jennifer Rieusset, Marie-Paule Gustin, Catherine Cerutti, Emmanuelle Meugnier, Emmanuel Disse, Aurélie Granjon, Christian Z. Paultre, Isabelle Güller, Martine Laville, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vericel, Evelyne, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Agressions vasculaires et réponses tissulaires, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie et Nutrition, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Diabetes Research Center, Montreal University, This work was supported by INRA and INSERM and a grant from ALFEDIAM-Roche., Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble
Subjects: Transcription, Genetic, Biopsy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Polymerase Chain Reaction, MESH: Glucose Clamp Technique, MESH: Down-Regulation, MESH: Biopsy, 0302 clinical medicine, Reference Values, Insulin, Myocyte, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, 0303 health sciences, MESH: Muscle, Skeletal, MEF2 Transcription Factors, MESH: Reference Values, MESH: Myogenic Regulatory Factors, Glucose clamp technique, MESH: Gene Expression Regulation, Cell biology, medicine.anatomical_structure, Myogenic Regulatory Factors, 030220 oncology & carcinogenesis, MESH: Hyperinsulinism, Original Article, Sterol Regulatory Element Binding Protein 1, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, DNA, Complementary, Down-Regulation, MESH: Insulin, Biology, Cell Line, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, Insulin resistance, Downregulation and upregulation, Hyperinsulinism, Internal medicine, Internal Medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, 030304 developmental biology, MESH: Humans, MESH: Transcription, Genetic, Skeletal muscle, MESH: Polymerase Chain Reaction, MESH: DNA, Complementary, medicine.disease, MESH: Cell Line, MicroRNAs, Insulin receptor, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Metabolism, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, Hyperglycemia, MESH: Oligonucleotide Array Sequence Analysis, Glucose Clamp Technique, biology.protein, MESH: Hyperglycemia, MESH: MicroRNAs, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: OBJECTIVE Factors governing microRNA expressions in response to changes of cellular environment are still largely unknown. Our aim was to determine whether insulin, the major hormone controlling whole-body energy homeostasis, is involved in the regulation of microRNA expressions in human skeletal muscle. RESEARCH DESIGN AND METHODS We carried out comparative microRNA (miRNA) expression profiles in human skeletal muscle biopsies before and after a 3-h euglycemic-hyperinsulinemic clamp, with TaqMan low-density arrays. Then, using DNA microarrays, we determined the response to insulin of the miRNA putative target genes in order to determine their role in the transcriptional action of insulin. We further characterized the mechanism of action of insulin on two representative miRNAs, miR-1 and miR-133a, in human muscle cells. RESULTS Insulin downregulated the expressions of 39 distinct miRNAs in human skeletal muscle. Their potential target mRNAs coded for proteins that were mainly involved in insulin signaling and ubiquitination-mediated proteolysis. Bioinformatic analysis suggested that combinations of different downregulated miRNAs worked in concert to regulate gene expressions in response to insulin. We further demonstrated that sterol regulatory element–binding protein (SREBP)-1c and myocyte enhancer factor 2C were involved in the effect of insulin on miR-1 and miR-133a expression. Interestingly, we found an impaired regulation of miRNAs by insulin in the skeletal muscle of type 2 diabetic patients, likely as consequences of altered SREBP-1c activation. CONCLUSIONS This work demonstrates a new role of insulin in the regulation of miRNAs in human skeletal muscle and suggests a possible implication of these new modulators in insulin resistance.
Published: 2009
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47. Increasing intakes of the long-chain ω-3 docosahexaenoic acid: effects on platelet functions and redox status in healthy men

Author: Emilie Caillet, Michel Lagarde, Nicolas Guillot, Evelyne Véricel, Catherine Calzada, Martine Laville, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, INSERM et contrat Groupe Lipides et Nutrition, Vericel, Evelyne, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Male, MESH: Oxidation-Reduction, Antioxidant, Isoprostane, genetic structures, medicine.medical_treatment, MESH: Dietary Supplements, vitamin E, isoprostane, Isoprostanes, 030204 cardiovascular system & hematology, medicine.disease_cause, p38 Mitogen-Activated Protein Kinases, Biochemistry, Antioxidants, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, 0302 clinical medicine, MESH: Vitamin E, MESH: Fatty Acids, Omega-3, oxidative stress, Platelet, MESH: Isoprostanes, Phospholipids, MESH: Blood Platelets, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, MESH: Aged, 0303 health sciences, MESH: Middle Aged, food and beverages, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, 3. Good health, MESH: Docosahexaenoic Acids, Docosahexaenoic acid, Arachidonic acid, lipids (amino acids, peptides, and proteins), Oxidation-Reduction, Biotechnology, Blood Platelets, medicine.medical_specialty, Docosahexaenoic Acids, 03 medical and health sciences, Internal medicine, Fatty Acids, Omega-3, Genetics, medicine, arachidonic acid, Humans, MESH: Platelet Activation, Molecular Biology, Aged, 030304 developmental biology, MESH: Phospholipids, MESH: Humans, Dose-Response Relationship, Drug, Vitamin E, MESH: Antioxidants, Fatty acid, Platelet Activation, MESH: Male, MESH: p38 Mitogen-Activated Protein Kinases, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Dietary Supplements, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oxidative stress
Abstract: International audience; Docosahexaenoic acid (DHA) can prevent cardiovascular events. However, few studies have addressed the effects of DHA on both platelet reactivity and redox status in healthy subjects, and dose-related studies are scarce. The main objectives of the present study were to determine the effects of increasing doses of DHA on platelets and redox status in humans. Twelve healthy male volunteers (aged 53-65 yr) were assigned to consume an intake of successively 200, 400, 800, and 1600 mg/d DHA, as the only omega-3 fatty acid, for 2 wk each dose. Blood and urine samples were collected before and after each dose of DHA and at 8 wk after arrest of supplementation. DHA was incorporated in a dose-response fashion in platelet phospholipids. After supplementation with 400 and 800 mg/d DHA, platelet reactivity was significantly decreased. Platelet vitamin E concentration increased only after 200 mg/d DHA, while p38 MAP kinase phosphorylation decreased. Urinary isoprostane was also significantly lowered after 200 mg/d DHA but was increased after 1600 mg/d. Therefore, supplementation with only 200 mg/d DHA for 2 wk induced an antioxidant effect. It is concluded that low consumption of DHA could be an effective and nonpharmacological way to protect healthy men from platelet-related cardiovascular events.
Published: 2009
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48. Plasma membrane microdomains from hybrid aspen cells are involved in cell wall polysaccharide biosynthesis

Author: Vincent Bulone, Soraya Djerbi, Nicolas Sindt, Michel Guichardant, Laurence Bessueille, Tuula T. Teeri, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), School of Biotechnology, Royal Institute of Technology [Stockholm] (KTH ), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Octoxynol, MESH: Membrane Microdomains, Biology, Hybrid Cells, Polysaccharide, Endocytosis, 01 natural sciences, Biochemistry, Trees, Cell wall, 03 medical and health sciences, chemistry.chemical_compound, Membrane Microdomains, MESH: Cell Wall, Biosynthesis, Cell Wall, Polysaccharides, MESH: Octoxynol, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Lipid raft, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, MESH: Glucosyltransferases, Callose, Cell Biology, Sphingolipid, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Trees, Membrane, MESH: Polysaccharides, chemistry, Glucosyltransferases, MESH: Hybrid Cells, 010606 plant biology & botany
Abstract: International audience; Detergent-resistant plasma membrane microdomains [DRMs (detergent-resistant membranes)] were isolated recently from several plant species. As for animal cells, a large range of cellular functions, such as signal transduction, endocytosis and protein trafficking, have been attributed to plant lipid rafts and DRMs. The data available are essentially based on proteomics and more approaches need to be undertaken to elucidate the precise function of individual populations of DRMs in plants. We report here the first isolation of DRMs from purified plasma membranes of a tree species, the hybrid aspen Populus tremula x tremuloides, and their biochemical characterization. Plasma membranes were solubilized with Triton X-100 and the resulting DRMs were isolated by flotation in sucrose density gradients. The DRMs were enriched in sterols, sphingolipids and glycosylphosphatidylinositol-anchored proteins and thus exhibited similar properties to DRMs from other species. However, they contained key carbohydrate synthases involved in cell wall polysaccharide biosynthesis, namely callose [(1-->3)-beta-D-glucan] and cellulose synthases. The association of these enzymes with DRMs was demonstrated using specific glucan synthase assays and antibodies, as well as biochemical and chemical approaches for the characterization of the polysaccharides synthesized in vitro by the isolated DRMs. More than 70% of the total glucan synthase activities present in the original plasma membranes was associated with the DRM fraction. In addition to shedding light on the lipid environment of callose and cellulose synthases, our results demonstrate the involvement of DRMs in the biosynthesis of important cell wall polysaccharides. This novel concept suggests a function of plant membrane microdomains in cell growth and morphogenesis.
Published: 2009
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49. Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men

Author: Michel Lagarde, Evelyne Véricel, Michel Guichardant, Nicolas Guillot, Catherine Calzada, Romain A. Colas, Martine Laville, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète', Groupe Lipides et Nutrition (GLN) and Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète'., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète',Agence Nationale de la Recherche (ANR) 2005 'Cardiovasculaire, Obésité et Diabète', Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vericel, Evelyne, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, n-3 Polyunsaturated fatty acids Antioxidant Peroxidation Low-density lipoproteins, MESH: Lipoproteins, LDL, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], alpha-Tocopherol, MESH: Dietary Supplements, MESH: Lipid Peroxidation, Antioxidants, Lipid peroxidation, Cohort Studies, chemistry.chemical_compound, MESH: Vitamin E, Malondialdehyde, Vitamin E, MESH: Cohort Studies, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Fatty Acids, food and beverages, MESH: Fatty Acids, Unsaturated, Middle Aged, Eicosapentaenoic acid, 3. Good health, MESH: Fatty Acids, MESH: Copper, Lipoproteins, LDL, MESH: Docosahexaenoic Acids, Biochemistry, MESH: alpha-Tocopherol, Docosahexaenoic acid, Low-density lipoprotein, Fatty Acids, Unsaturated, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, MESH: Oxygen, Polyunsaturated fatty acid, medicine.medical_specialty, Docosahexaenoic Acids, MESH: Malondialdehyde, 03 medical and health sciences, Internal medicine, medicine, Humans, Unsaturated fatty acid, 030304 developmental biology, Aged, MESH: Humans, MESH: Antioxidants, MESH: Male, Oxygen, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Dietary Supplements, Lipid Peroxidation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Copper, Lipoprotein
Abstract: International audience; OBJECTIVE: To determine the effect of supplementation with increasing doses of docosahexaenoic acid (DHA), as the only n-3 polyunsaturated fatty acid (PUFA), on low-density lipoprotein (LDL) redox status and oxidizability. METHODS: Twelve healthy men aged 53-65 years ingested consecutive doses of DHA (200, 400, 800 and 1600 mg/day), each dose for two weeks. RESULTS: The proportions of DHA increased dose-dependently in LDL phospholipids and cholesteryl esters, even after two weeks of supplementation with 200mg/day DHA. The daily intake of 200, 400 and 800 mg DHA resulted in increased alpha-tocopherol concentrations, decreased MDA concentrations, and a longer lag time for copper-induced LDL oxidation. Supplementation with 1600 mg/day DHA had no effect on the above parameters. In plasma, concentrations of 4-hydroxy-hexenal, specifically derived from the peroxidation of n-3 fatty acids, significantly increased after 800 and 1600 mg DHA, representing 0.01% of plasma n-3 PUFAs, while 4-hydroxy-nonenal concentrations, derived from the peroxidation of n-6 fatty acids, did not change. CONCLUSION: Our results clearly show that an intake of 200-800 mg/day DHA may have protective and antioxidant effects on LDL and could represent optimal doses for cardiovascular disease prevention in a healthy population.
Published: 2009
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50. Cell wall polysaccharide synthases are located in detergent-resistant membrane microdomains in oomycetes

Author: Laurence Bessueille, Anne Briolay, Michel Guichardant, Nicolas Sindt, Christian Deshayes, Vincent Bulone, Jamel Bouzenzana, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Algal Proteins, MESH: Membrane Microdomains, Mycology, Saprolegnia, Polysaccharide, Cellulose synthase activity, Applied Microbiology and Biotechnology, Cell wall, 03 medical and health sciences, chemistry.chemical_compound, Membrane Microdomains, Biosynthesis, Chitin, MESH: Saprolegnia, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Lipid raft, 030304 developmental biology, chemistry.chemical_classification, Chitin Synthase, 0303 health sciences, MESH: Glucosyltransferases, Ecology, biology, 030302 biochemistry & molecular biology, Algal Proteins, Chitin synthase, MESH: Chitin Synthase, Yeast, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Biochemistry, chemistry, Glucosyltransferases, biology.protein, lipids (amino acids, peptides, and proteins), Food Science, Biotechnology
Abstract: The pathways responsible for cell wall polysaccharide biosynthesis are vital in eukaryotic microorganisms. The corresponding synthases are potential targets of inhibitors such as fungicides. Despite their fundamental and economical importance, most polysaccharide synthases are not well characterized, and their molecular mechanisms are poorly understood. With the example ofSaprolegnia monoicaas a model organism, we show that chitin and (1→3)-β-d-glucan synthases are located in detergent-resistant membrane microdomains (DRMs) in oomycetes, a phylum that comprises some of the most devastating microorganisms in the agriculture and aquaculture industries. Interestingly, no cellulose synthase activity was detected in the DRMs. The purified DRMs exhibited similar biochemical features as lipid rafts from animal, plant, and yeast cells, although they contained some species-specific lipids. This report sheds light on the lipid environment of the (1→3)-β-d-glucan and chitin synthases, as well as on the sterol biosynthetic pathways in oomycetes. The results presented here are consistent with a function of lipid rafts in cell polarization and as platforms for sorting specific sets of proteins targeted to the plasma membrane, such as carbohydrate synthases. The involvement of DRMs in the biosynthesis of major cell wall polysaccharides in eukaryotic microorganisms suggests a function of lipid rafts in hyphal morphogenesis and tip growth.
Published: 2009
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