Search

Your search keyword '"Vericel, Evelyne"' showing total 83 results
Start Over Author "Vericel, Evelyne"
83 results on '"Vericel, Evelyne"'

2. Diabetic patients without vascular complications display enhanced basal platelet activation and decreased antioxidant status

Author

Vericel, Evelyne, Januel, Caroline, Carreras, Martine, Moulin, Philippe, and Lagarde, Michel

Subjects
Diabetes -- Care and treatment -- Research, Blood platelets -- Research -- Activation, Blood circulation disorders -- Care and treatment -- Research, Health, Care and treatment, Research
Abstract

Vascular complications are the leading causes of morbidity and mortality in diabetic patients. The contribution of platelets to thromboembolic complications is well documented, but their involvement in the initiation of the atherosclerotic process is of rising interest. Thus, the aim of the present study was to evaluate basal arachidonic acid metabolism in relation to the redox status of platelets in both type 1 and type 2 diabetic patients, in the absence of vascular complications, as compared with respective control subjects. For the first time, we show that basal thromboxane [B.sub.2], the stable catabolite of thromboxane [A.sub.2], significantly increased in resting platelets from both type 1 and type 2 diabetic patients (58 and 88%, respectively), whereas platelet malondialdehyde level was only higher in platelets from type 2 diabetic subjects (67%). On the other hand, both vitamin E levels and cytosolic glutathione peroxidase activities were significantly lower in platelets from diabetic patients as compared with respective control subjects. We conclude that platelet hyperactivation was detectable in well-controlled diabetic patients without complications. This abnormality was associated with increased oxidative stress and impaired antioxidant defense in particular in type 2 diabetic patients. These alterations contribute to the increased risk for occurrence of vascular diseases in such patients., Diabetes is associated with accelerated rates of thrombosis, circulation dysfunction, and atherosclerosis, and it is fully recognized that long-term macrovascular complications are the main cause of morbidity and mortality associated [...]

Published
2004

5. Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity

Author

Brault, Charlene, Levy, Pierre, Duponchel, Sarah, Michelet, Maud, Salle, Aurelie, Pecheur, Eve-Isabelle, Plissonnier, Marie-Laure, Parent, Romain, Vericel, Evelyne, Ivanov, Alexander V., Demir, Muenevver, Steffen, Hans-Michael, Odenthal, Margarete, Zoulim, Fabien, Bartosch, Birke, Brault, Charlene, Levy, Pierre, Duponchel, Sarah, Michelet, Maud, Salle, Aurelie, Pecheur, Eve-Isabelle, Plissonnier, Marie-Laure, Parent, Romain, Vericel, Evelyne, Ivanov, Alexander V., Demir, Muenevver, Steffen, Hans-Michael, Odenthal, Margarete, Zoulim, Fabien, and Bartosch, Birke

Abstract

Objective Inflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it eliminates ROS is less well known. The role of the ROS scavenger glutathione peroxidase 4 (GPx4), induced by HCV, in the viral life cycle was analysed. Design The study was performed using a replicative in vitro HCV infection model and liver biopsies derived from two different CHC patient cohorts. Results A screen for HCV-induced peroxide scavengers identified GPx4 as a host factor required for HCV infection. The physiological role of GPx4 is the elimination of lipid peroxides from membranes or lipoproteins. GPx4-silencing reduced the specific infectivity of HCV by up to 10-fold. Loss of infectivity correlated with 70% reduced fusogenic activity of virions in liposome fusion assays. NS5A was identified as the protein that mediates GPx4 induction in a phosphatidylinositol-3-kinase-dependent manner. Levels of GPx4 mRNA were found increased in vitro and in CHC compared with control liver biopsies. Upon successful viral eradication, GPx4 transcript levels returned to baseline in vitro and also in the liver of patients. Conclusions HCV induces oxidative stress but controls it tightly by inducing ROS scavengers. Among these, GPx4 plays an essential role in the HCV life cycle. Modulating oxidative stress in CHC by specifically targeting GPx4 may lower specific infectivity of virions and prevent hepatocarcinogenesis, especially in patients who remain difficult to be treated in the new era of interferon-free regimens.

Published
2016

12. Biological relevance of double lipoxygenase products of polyunsaturated fatty acids, especially within blood vessels and brain

Author

Michel Lagarde, Michel Guichardant, Evelyne Véricel, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), The authors want to thank Inserm, Inra and the Ministry of Research through INSA-Lyon for their continuous support. Part of the original work supporting this review has been done by Drs Ping Chen and Miao Liu during their PhD thesis in our laboratory., Vericel, Evelyne, 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
0301 basic medicine, Docosahexaenoic Acids, Protectins, Protectin D1, Biochemistry, 03 medical and health sciences, Hydrolysis, chemistry.chemical_compound, Lipoxygenase, Stereochemistry, Omega-3 fatty acids, Humans, Platelet aggregation, chemistry.chemical_classification, 030102 biochemistry & molecular biology, biology, alpha-Linolenic acid, Linotrins, Brain, alpha-Linolenic Acid, food and beverages, General Medicine, Lipoxygenases, Metabolic pathway, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, chemistry, Docosahexaenoic acid, biology.protein, Blood Vessels, lipids (amino acids, peptides, and proteins), Cyclooxygenase, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Polyunsaturated fatty acid
Abstract

International audience; The double lipoxygenation of polyunsaturated fatty acids (PUFA) is possible with PUFA having at least three methylene-interrupted double bonds. Several PUFA of the omega-3/n-3 and -6 families may be converted through this route, and the products show interesting inhibitory effects on blood platelet function and cyclooxygenase activities. This review focuses on two main omega-3 PUFA of nutritional interest, namely docosahexaenoic acid (DHA/22:6n-3) and alpha linolenic acid (ALA/18:3n-3). The chemical configuration of the double lipoxygenase end-product from DHA (protectin DX) is compared with that of protectin D1 which is produced through a mono-lipoxygenation step followed by an epoxidation and epoxide hydrolysis process. The different metabolic pathways are discussed as well as the different biological activities of both protectins.

Published
2019
Full Text
View/download PDF

13. Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets

Author

Michel Lagarde, Michel Guichardant, Catherine Calzada, Evelyne Véricel, Nathalie Bernoud-Hubac, 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), Inserm and the Ministry of Research., 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), Inserm, Ministry of Research, and Vericel, Evelyne

Subjects
Blood Platelets, 0301 basic medicine, medicine.medical_specialty, Aging, Peroxidation, 030204 cardiovascular system & hematology, Arachidonate 12-Lipoxygenase, 03 medical and health sciences, chemistry.chemical_compound, Thromboxane A2, 0302 clinical medicine, Phospholipase A2, Internal medicine, Octadecanoids, medicine, Animals, Humans, Platelet, Platelet aggregation, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, biology, Diabetes, food and beverages, Cell Biology, Eicosapentaenoic acid, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Oxidative Stress, 030104 developmental biology, Endocrinology, chemistry, Docosahexaenoic acid, Docosanoids, Cyclooxygenase 1, Fatty Acids, Unsaturated, biology.protein, Eicosanoids, Arachidonic acid, lipids (amino acids, peptides, and proteins), Cyclooxygenase, Oxidation-Reduction, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Polyunsaturated fatty acid
Abstract

International audience; The oxygenation metabolism of arachidonic acid (ArA) has been early described in blood platelets, in particular with its conversion into the potent labile thromboxane A(2) that induces platelet aggregation and vascular smooth muscle cells contraction. In addition, the primary prostaglandins D-2 and E-2 have been mainly reported as inhibitors of platelet function. The platelet 12-lipoxygenase (12-LOX) product, i.e. the hydroperoxide 12-HpETE, appears to stimulate platelet ArA metabolism at the level of its release from membrane phospholipids through phospholipase A(2) (cPLA(2)) and cyclooxygenase (COX-1) activities, the first enzymes in prostanoid production cascade. Also, 12-HpETE may regulate the oxygenation of other polyunsaturated fatty acids (PUFA) by platelets, especially that of eicosapentaenoic acid (EPA). On the other hand, the reduced product of 12-HpETE, 12-HETE, is able to antagonize TxA(2) action. This is even more obvious for the 12-LOX end-products from docosahexaenoic acid (DHA), 11- and 14-HDoHE. In addition, 12-HpETE plays a key role in platelet oxidative stress as observed in pathophysiological conditions, but may be regulated by DHA with a bimodal way according to its concentration. Other oxygenated products of PUFA, especially omega-3 PUFA, produced outside platelets may affect platelet functions as well.

Published
2018
Full Text
View/download PDF

14. Dose-effect and metabolism of docosahexaenoic acid: Pathophysiological relevance in blood platelets

Author

Michel Lagarde, Michel Guichardant, Catherine Calzada, Evelyne Véricel, 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), The authors thank the support of INSERM, the Ministry of Education and Research, and the LISA Carnot Institute, 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), and Vericel, Evelyne

Subjects
Blood Platelets, Antioxidant, Docosahexaenoic Acids, Platelet Aggregation, Thromboxane, medicine.medical_treatment, Clinical Biochemistry, 030204 cardiovascular system & hematology, Biology, Pharmacology, Antioxidants, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, Lipoxygenase, 0302 clinical medicine, medicine, Animals, Humans, Platelet, 030304 developmental biology, 0303 health sciences, food and beverages, Cell Biology, Lipoxygenases, Oxidants, lipoxygenase, 3. Good health, Lipoproteins, LDL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, Biochemistry, Docosahexaenoic acid, Dietary Supplements, biology.protein, Platelet aggregation inhibitor, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, Cyclooxygenase, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Platelet Aggregation Inhibitors
Abstract

International audience; Docosahexaenoic acid (DHA) is known as a major nutrient from marine origin. Considering its beneficial effect in vascular risk prevention, the effect of DHA on blood components, especially platelets, will be reviewed here. Investigating the dose-effect of DHA in humans shows that daily intake lower than one gram/day brings several benefits, such as inhibition of platelet aggregation, resistance of monocytes against apoptosis, and reinforced antioxidant status in platelets and low-density lipoproteins. However, higher daily intake may be less efficient on those parameters, especially by losing the antioxidant effect. On the other hand, a focus on the inhibition of platelet aggregation by lipoxygenase end-products of DHA is made. The easy conversion of DHA by lipoxygenases and the formation of a double lipoxygenation product named protectin DX, reveal an original way for DHA to contribute in platelet inhibition through both the cyclooxygenase inhibition and the antagonism of thromboxane A(2) action.

Published
2013
Full Text
View/download PDF

15. Moderate intake of docosahexaenoic acid raises plasma and platelet vitamin E levels in cystic fibrosis patients

Author

Stéphane Mazur, Michel Lagarde, Romain Colas, Véronique Delaup, Philippe Reix, Evelyne Véricel, Isabelle Durieu, Gabriel Bellon, Catherine Calzada, 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), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Médecine Interne - Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Nice Sophia Antipolis - Faculté de Chirurgie Dentaire (UNS UFR Odontologie), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service de Pneumologie Pédiatrique, Hospices Civils de Lyon (HCL)-Hôpital Debrousse, Inserm, Association 'Vaincre la mucoviscidose', Vericel, Evelyne, 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 Nice Sophia Antipolis (1965 - 2019) (UNS), 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), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)

Subjects
Adult, Blood Platelets, Male, 0301 basic medicine, medicine.medical_specialty, Antioxidant, Adolescent, Cystic Fibrosis, Docosahexaenoic Acids, genetic structures, medicine.medical_treatment, Clinical Biochemistry, Placebo, medicine.disease_cause, Cystic fibrosis, antioxidant status, Drug Administration Schedule, platelet lipid, Lipid peroxidation, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Double-Blind Method, Internal medicine, medicine, Humans, Vitamin E, oxidative stress, Child, plasma, Cross-Over Studies, business.industry, food and beverages, Cell Biology, docosahexaenoic acid, medicine.disease, 3. Good health, Thromboxane B2, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Endocrinology, chemistry, Docosahexaenoic acid, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oxidative stress
Abstract

International audience; Patients with cystic fibrosis have increased oxidative stress and impaired antioxidant systems. Moderate intake of docosahexaenoic acid (DHA) may favor the lowering of oxidative stress. In this randomized, double-blind, cross-over study, DHA or placebo capsules, were given daily to 10 patients, 5 mg/kg for 2 weeks then 10 mg/kg DHA for the next 2 weeks (or placebo). After 9 weeks of wash-out, patients took placebo or DHA capsules. Biomarkers of lipid peroxidation and vitamin E were measured at baseline, and after 2 and 4 weeks of treatment in each phase. The proportions of DHA increased both in plasma and platelet lipids after DHA supplementations. The lipid peroxidation markers did not significantly decrease, in spite of a trend, after the first and/or the second dose of DHA but plasma and platelet vitamin E amounts increased significantly after DHA supplementation. Our findings reinforce the antioxidant potential of moderate DHA intake in subjects displaying increased oxidative stress.

Published
2016
Full Text
View/download PDF

16. FTO Is Increased in Muscle During Type 2 Diabetes, and Its Overexpression in Myotubes Alters Insulin Signaling, Enhances Lipogenesis and ROS Production, and Induces Mitochondrial Dysfunction

Author

Jennifer Rieusset, Hubert Vidal, Noël Peretti, Amélie Bravard, Julien Vouillarmet, Rémi Rabasa-Lhoret, Martine Laville, Etienne Lefai, Emmanuelle Meugnier, Sandra Pesenti, Emmanuel Disse, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), 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 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, Montreal Diabetes Research Center, Montreal University, This work was supported by grants from INSERM and ANR (grant ANR-09-JCJC-0116-01 to J.R.). A.B. is a recipient of a grant from Servier Laboratories and ANRT. GlaxoSmithKline sponsored the rosiglitazone treatment study., Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), 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-Université Joseph Fourier - Grenoble 1 (UJF), 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]), and Vericel, Evelyne

Subjects
Blood Glucose, Male, MESH: Signal Transduction, Biopsy, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Muscle Fibers, Skeletal, VARIANTS, MESH: Thiazolidinediones, MESH: Biopsy, Adenosine Triphosphate, 0302 clinical medicine, MESH: Genetic Vectors, MESH: Adenosine Triphosphate, ADULT OBESITY, Insulin, MESH: Proteins, OXIDATIVE STRESS, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, GENE-EXPRESSION, MESH: Muscle, Skeletal, 0303 health sciences, MESH: Middle Aged, MESH: Muscle Fibers, Skeletal, MESH: Oxidative Stress, biology, Myogenesis, MESH: Mitochondria, Muscle, MESH: Reactive Oxygen Species, HUMANS, Middle Aged, HUMAN SKELETAL-MUSCLE, MESH: Gene Expression Regulation, ADIPOSE-TISSUE, FAT MASS, medicine.anatomical_structure, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Lipogenesis, MESH: Hemoglobin A, Glycosylated, Female, MESH: Diabetes Mellitus, Type 1, Rosiglitazone, Signal Transduction, MESH: Diabetes Mellitus, Type 2, medicine.drug, medicine.medical_specialty, Genetic Vectors, 030209 endocrinology & metabolism, MESH: Insulin, Pathophysiology, 03 medical and health sciences, MESH: RNA, MESH: Hypoglycemic Agents, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Hypoglycemic Agents, Muscle, Skeletal, 030304 developmental biology, Glycated Hemoglobin, MESH: Humans, Proteins, nutritional and metabolic diseases, Skeletal muscle, medicine.disease, MESH: Male, Mitochondria, Muscle, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Insulin receptor, Diabetes Mellitus, Type 1, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, CELLS, MESH: Oligonucleotide Array Sequence Analysis, MESH: Blood Glucose, biology.protein, RNA, Thiazolidinediones, Reactive Oxygen Species, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, RESISTANCE
Abstract

OBJECTIVE A strong association between genetic variants and obesity was found for the fat mass and obesity-associated gene (FTO). However, few details are known concerning the expression and function of FTO in skeletal muscle of patients with metabolic diseases. RESEARCH DESIGN AND METHODS We investigated basal FTO expression in skeletal muscle from obese nondiabetic subjects and type 1 and type 2 diabetic patients, compared with age-matched control subjects, and its regulation in vivo by insulin, glucose, or rosiglitazone. The function of FTO was further studied in myotubes by overexpression experiments. RESULTS We found a significant increase of FTO mRNA and protein levels in muscle from type 2 diabetic patients, whereas its expression was unchanged in obese or type 1 diabetic patients. Moreover, insulin or glucose infusion during specific clamps did not regulate FTO expression in skeletal muscle from control or type 2 diabetic patients. Interestingly, rosiglitazone treatment improved insulin sensitivity and reduced FTO expression in muscle from type 2 diabetic patients. In myotubes, adenoviral FTO overexpression increased basal protein kinase B phosphorylation, enhanced lipogenesis and oxidative stress, and reduced mitochondrial oxidative function, a cluster of metabolic defects associated with type 2 diabetes. CONCLUSIONS This study demonstrates increased FTO expression in skeletal muscle from type 2 diabetic patients, which can be normalized by thiazolidinedione treatment. Furthermore, in vitro data support a potential implication of FTO in oxidative metabolism, lipogenesis and oxidative stress in muscle, suggesting that it could be involved in the muscle defects that characterize type 2 diabetes.

Published
2010
Full Text
View/download PDF

17. 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
Full Text
View/download PDF

18. 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
Full Text
View/download PDF

19. Fatty acids platelets and oxidative markers following intravenous n-3 fatty acids administration in cystic fibrosis: An open pilot observational study

Author

Gabriel Bellon, Hubert Roth, Michel Lagarde, Isabelle Durieu, Evelyne Véricel, Raphaele Nove Josserand, Jocelyne Drai, Daniel Guichardant, Jean-Paul Steghens, Eric Fontaine, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Physiopathologie des Lipides et Membranes (PLM), 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)-Centre National de la Recherche Scientifique (CNRS), Bioénergétique fondamentale et appliquée, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Biochimie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Service de Biochimie Générale, Métabolique et Moléculaire, Centre de Ressources et de compétences de la mucoviscidose (CRCM), Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Vericel, Evelyne, Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Oxidation-Reduction, 030309 nutrition & dietetics, Pilot Projects, 030204 cardiovascular system & hematology, medicine.disease_cause, Cystic fibrosis, Lipid peroxidation, chemistry.chemical_compound, 0302 clinical medicine, MESH: Fatty Acids, Omega-3, Weight loss, MESH: Child, Platelet, Child, MESH: Blood Platelets, Intravenous fish-oil treatment, 0303 health sciences, Fatty Acids, n-3 fatty acids, MESH: Fatty Acids, 3. Good health, Biochemistry, Docosahexaenoic acid, Child, Preschool, Injections, Intravenous, Arachidonic acid, medicine.symptom, Oxidation-Reduction, Adult, Blood Platelets, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, MESH: Cystic Fibrosis, 03 medical and health sciences, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Pediatrics, Perinatology, and Child Health, MESH: Adolescent, Glutathione Peroxidase, MESH: Humans, business.industry, MESH: Child, Preschool, MESH: Biological Markers, MESH: Adult, Glutathione, MESH: Pilot Projects, medicine.disease, MESH: Injections, Intravenous, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Oxidative stress, MESH: Glutathione Peroxidase, Pediatrics, Perinatology and Child Health, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract

International audience; BACKGROUND: An imbalance in the ratio of arachidonic acid and docosahexaenoic acid (DHA) was found in cystic fibrosis (CF) affected tissues and was suggested to promote inflammation. Several studies have shown that the long chain n-3 fatty acids reduced inflammatory activity while others have highlighted prooxidant activity of DHA at high concentrations. The aim of our study was to evaluate the effects of an intravenous fish-oil emulsion enriched with n-3 FA in patients with CF on plasma and platelet FA composition and peroxidation markers. METHODS: 13 patients with CF received one IV emulsion per week of 2 mL/kg fish-oil n-3 emulsion for 12 weeks. RESULTS: There was a significant increase in 20:5 n-3 and 22:6 n-3 platelet FA composition, no variation in 20:4 n-6, a decrease in n-9. There was no variation in plasma FA composition. Specific urinary markers of lipid peroxidation derived from n-3 and n-6 showed a very high level before infusion compared with usual values in healthy subjects which was not affected by treatment. A significant weight loss and a decrease in reduced glutathione were observed in adult patients. CONCLUSIONS: The intravenous administration of n-3 FA in CF patients induced a significant modification in platelet FA composition but no modification of oxidative markers. However, the weight loss and the decreased level in reduced glutathione observed in adult patients may suggest a potential deleterious activity for some patients. Further studies are necessary to determine the optimal dose and route for long chain FA administration required to reach a potential beneficial effect.

Published
2007
Full Text
View/download PDF

20. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function

Author

Michel Lagarde, Catherine Calzada, Philippe Moulin, Michel Guichardant, Meddy El Alaoui, Evelyne Véricel, Laurent Soulère, B. Segrestin, Quang Huy Lê, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie Organique et Bioorganique (COB), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 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-Institut de Chimie du CNRS (INC)-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-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), Fédération d'Endocrinologie, Hospices Civils de Lyon (HCL), Inserm, French Ministry of Education and Research, Région Rhône Alpes and CNRS., Vericel, Evelyne, Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-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 de Chimie du CNRS (INC)-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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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)-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)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Antioxidant, Platelet Aggregation, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Type 2 diabetes, 030204 cardiovascular system & hematology, p38 Mitogen-Activated Protein Kinases, Biochemistry, chemistry.chemical_compound, hydroxy - octadecadienoic acid, 0302 clinical medicine, Endocrinology, Platelet, Phospholipids, 0303 health sciences, Middle Aged, 3. Good health, platelets, Female, Arachidonic acid, lipids (amino acids, peptides, and proteins), oxidized phospholipids, Lipoproteins, HDL, Signal Transduction, Adult, Blood Platelets, medicine.medical_specialty, Context (language use), Article, Young Adult, 03 medical and health sciences, Diabetes mellitus, Internal medicine, medicine, Humans, Aged, 030304 developmental biology, High density lipoproteins, Dose-Response Relationship, Drug, diabetes, Biochemistry (medical), nutritional and metabolic diseases, Platelet Activation, medicine.disease, In vitro, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, chemistry, Calcium, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Function (biology)
Abstract

International audience; CONTEXT:High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D).OBJECTIVE:The objective of our study was to investigate the effects of in vitro glycoxidized HDL, and HDL from T2D patients on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL.RESULTS:Compared to control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to SR-BI. Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phospholipids, namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE and 15-HETE in phospholipids (2.1, 2.1 and 2.4-fold increase respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI.CONCLUSIONS:Altogether, our results indicate that in vitro glycoxidized HDL as well as HDL from T2D patients inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from T2D patients.

Published
2015
Full Text
View/download PDF

21. Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients: DHA amends platelet function and redox status

Author

Véricel, Evelyne, Colas, Romain, Calzada, Catherine, Lê, Quang Huy, Feugier, Nathalie, Cugnet, Christine, Vidal, Hubert, Laville, Martine, Moulin, Philippe, Lagarde, Michel, Vericel, Evelyne, 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)-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-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]), Endocrinologie et diabétologie B, Hôpitaux Est Hôpital Louis Pradel - Hospices Civils de Lyon, and This work was supported by Inserm and a grant from the Fondation Cœur & Artères.

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, plasma and platelet lipid composition, arachidonic acid, Platelet aggregation, isoprostane, vitamin E, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Platelets from patients with type 2 diabetes are characterized by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for 2 weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each 2 week-period was separated from the other by a 6-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5%, p

Published
2015
Full Text
View/download PDF

22. Structure-function relationships of non-cyclic dioxygenase products from polyunsaturated fatty acids: Poxytrins as a class of bioactive derivatives

Author

Michel Guichardant, Michel Lagarde, Ping Chen, Evelyne Véricel, Miao Liu, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Vericel, Evelyne

Subjects
Docosahexaenoic Acids, Platelet Aggregation, Stereochemistry, Conjugated system, Biochemistry, cyclo-oxygenases, Dioxygenases, Structure-Activity Relationship, 03 medical and health sciences, Lipoxygenase, 0302 clinical medicine, Dioxygenase, leukotrienes, Fatty Acids, Omega-3, Humans, prostanoids, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Molecular Structure, biology, Chemistry, Structure function, alpha-Linolenic Acid, Stereoisomerism, General Medicine, lipoxygenases, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Docosahexaenoic acid, Protectin DX, 030220 oncology & carcinogenesis, Fatty Acids, Unsaturated, biology.protein, Cyclooxygenase, blood cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Polyunsaturated fatty acid
Abstract

International audience; : More and more attention is paid to omega-3 fatty acids because of their potential activities in preventing cardiovascular events. In this brief review, we focus on the lipoxygenase end-metabolites of two relevant nutrients belonging to the omega-3 family fatty acids: alpha-linolenic and docosahexaenoic acids, the latter being a prominent component of brain lipids. Dihydroxylated derivatives are described as well as their inhibitory effects on platelet aggregation and cyclooxygenase activities. We point out that only the dihydroxylated products with the trans,cis,trans/E,Z,E conjugated triene geometry exhibit those inhibitory activities. These properties being found with other polyunsaturated fatty acid oxygenated products sharing the same E,Z,E molecular motif, they have been collectively named poxytrins. From alpha-linolenic and docosahexaenoic acids, poxytrins are linotrins and protectin DX, respectively.

Published
2014
Full Text
View/download PDF

23. Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis

Author

Michel Guichardant, Michel Lagarde, Evelyne Véricel, Catherine Calzada, Nathalie Bernoud-Hubac, 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), The support of Inserm and INRA,the French Ministry of Higher Education andResearch, the LISA Carnot Institute and the IBiSAFunctional Lipidomics platform isgreatly acknowledged., Vericel, Evelyne, 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
eicosapentaenoic acid, Antioxidant, Docosahexaenoic Acids, medicine.medical_treatment, 030204 cardiovascular system & hematology, Biology, Pharmacology, Risk Assessment, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Fatty Acids, Omega-3, medicine, Animals, Humans, Platelet activation, dioxygenases, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Dose-Response Relationship, Drug, alpha-Linolenic acid, food and beverages, Cardiovascular Agents, Thrombosis, Cell Biology, Metabolism, docosahexaenoic acid, Atherosclerosis, Isoprostanes, Eicosapentaenoic acid, peroxidation, 3. Good health, alpha-linolenic acid, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Treatment Outcome, Biochemistry, chemistry, Docosahexaenoic acid, platelets, lipids (amino acids, peptides, and proteins), Oxidation-Reduction, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Polyunsaturated fatty acid
Abstract

Numerous epidemiological studies and clinical trials have reported the health benefits of omega-3 polyunsaturated fatty acids (PUFA), including a lower risk of coronary heart diseases. This review mainly focuses on the effects of alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on some risk factors associated with atherothrombosis, including platelet activation, plasma lipid concentrations and oxidative modification of low-density lipoproteins (LDL). Special focus is given to the effects of marine PUFA on the formation of eicosanoids and docosanoids, and to the bioactive properties of some oxygenated metabolites of omega-3 PUFA produced by cyclooxygenases and lipoxygenases. The antioxidant effects of marine omega-3 PUFA at low concentrations and the pro-oxidant effects of DHA at high concentrations on the redox status of platelets and LDL are highlighted. Non enzymatic peroxidation end-products deriving from omega-3 PUFA such as hydroxy-hexenals, neuroketals and EPA-derived isoprostanes are also considered in relation to atherosclerosis. This article is part of a Special Issue entitled “Oxygenated metabolism of PUFA: analysis and biological relevance”.

Published
2014
Full Text
View/download PDF

24. Biological properties of a DHA-containing structured phospholipid (AceDoPC) to target the brain

Author

Michel Guichardant, Nathalie Bernoud-Hubac, Michel Lagarde, Madeleine Picq, Evelyne Véricel, Mayssa Hachem, 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), and Vericel, Evelyne

Subjects
genetic structures, Clinical Biochemistry, Phospholipid, Biology, Blood–brain barrier, chemistry.chemical_compound, Blood plasma, medicine, Animals, Humans, Platelet, Platelet activation, Phospholipids, Platelet-activating factor, Brain, food and beverages, Transporter, Cell Biology, blood-brain barrier, stroke, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, Neuroprotective Agents, chemistry, Biochemistry, Docosahexaenoic acid, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; : 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC) has been made to prevent docosahexaenoyl (DHA) to move to the sn-1 position as it rapidly does when present in 1-lyso,2-docosahexaenoyl-GPC (lysoPC-DHA), an efficient DHA transporter to the brain. When incubated with human blood, AceDoPC behaves closer to lysoPC-DHA than PC-DHA in terms of binding to plasma albumin and lipoproteins, and DHA incorporation into platelets and red cells. In addition, AceDoPC prevents more efficiently the deleterious effects of the experimental stroke in rats than does unesterified DHA. Also, AceDoPC inhibits platelet-activating factor-induced human blood platelet aggregation. Overall, AceDoPC might act as an efficient DHA transporter to the brain, and as a neuro-protective agent by itself.

Published
2014
Full Text
View/download PDF

25. pH-dependent Formation of Membranous Cytoplasmic Body-Like Structure of Ganglioside GM1/Bis(Monoacylglycero)Phosphate Mixed Membranes

Author

Hiroshi Takahashi, Asami Makino, Hirotami Matsuo, Motohide Murate, Tetsuro Fujisawa, Toshihide Kobayashi, Kazuki Ito, Ichiro Sugimoto, Yasuhiro Hashimoto, Tomohiro Hayakawa, Lipid Biology Laboratory, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Supra-Biomolecular System Research Group, Department of Physics, Gunma University, RIKEN SPring-8 Center [Hyogo] (RIKEN RSC), School of Pharmacy, Shujitsu University, Physiopathologie des Lipides et Membranes (PLM), 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-Centre National de la Recherche Scientifique (CNRS), Vericel, Evelyne, Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
late endosome, MESH: Hydrogen-Ion Concentration, Cytoplasm, Biophysical Letters, Gangliosidosis, Micelle, chemistry.chemical_compound, MESH: Cholesterol, 0302 clinical medicine, Gangliosides, Lamellar structure, Micelles, Late endosome, 0303 health sciences, MESH: G(M1) Ganglioside, Chemistry, Vesicle, MESH: Models, Chemical, MESH: Micelles, Hydrogen-Ion Concentration, gangliosidosis, Cholesterol, Membrane, freeze fracture electron microscopy, Monoglycerides, lipids (amino acids, peptides, and proteins), MESH: Monoglycerides, Biophysics, G(M1) Ganglioside, MESH: Lysophospholipids, 03 medical and health sciences, small-angle x-ray scattering, medicine, Humans, MESH: Biophysics, MESH: Gangliosides, 030304 developmental biology, MESH: Humans, Ganglioside, MESH: Cytoplasm, Fibroblasts, medicine.disease, Sialic acid, carbohydrates (lipids), [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Crystallography, Models, Chemical, MESH: Fibroblasts, lysobisphosphatidic acid, Lysophospholipids, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

International audience; Membrane structures of the mixtures of ganglioside G(M1) and endosome specific lipid, bis (monoacylglycero) phosphate (BMP, also known as lysobisphosphatidic acid) were examined at various pH conditions by freeze-fracture electron microscopy and small-angle x-ray scattering. At pH 8.5-6.5, a G(M1)/BMP (1:1 mol/mol) mixture formed small vesicular aggregates, whereas the mixture formed closely packed lamellar structures under acidic conditions (pH 5.5, 4.6) with the lamellar repeat distance of 8.06 nm. Since BMP alone exhibits a diffuse lamellar structure at a broad range of pH values and G(M1) forms a micelle, the results indicate that both G(M1) and BMP are required to produce closely stacked multilamellar vesicles. These vesicles resemble membranous cytoplasmic bodies in cells derived from patients suffering from G(M1) gangliosidosis. Similar to G(M1) gangliosidosis, cholesterol was trapped in BMP vesicles in G(M1)- and in a low pH-dependent manner. Studies employing different gangliosides and a G(M1) analog suggest the importance of sugar chains and a sialic acid of G(M1) in the pH-dependent structural change of G(M1)/BMP membranes.

Published
2007
Full Text
View/download PDF

26. Docosahexaenoic acid, protectin synthesis: relevance against atherothrombogenesis.: DHA & protectins against atherothrombosis

Author

Lagarde, Michel, Liu, Miao, Véricel, Evelyne, Calzada, Catherine, Chen, Ping, Driss, Fathi, Guichardant, Michel, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm, Ministry of Education and Research, ANR, and Carnot LISA institute., and Vericel, Evelyne

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Blood platelets, Leukocytes, lipids (amino acids, peptides, and proteins), Lipoxygenases, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cyclooxygenases
Abstract

International audience; DHA is an abundant nutrient from marine lipids: its specific biological effects have been investigated in human volunteers, taking into consideration the dose effects. We report herein that, at dosages below 1 g/d, DHA proved to be effective in lowering blood platelet function and exhibited an 'antioxidant' effect. However, this was no longer the case following 1*6 g/d, showing then a U-shape response. The antioxidant effect has been observed in platelets as well as LDL, of which the redox status is assumed to be crucial in their relationship with atherosclerosis. Second, the oxygenated products of DHA, especially protectins produced by lipoxygenases, have been considered for their potential to affect blood platelets and leucocytes. It is concluded that DHA is an interesting nutrient to reduce atherothrombogenesis, possibly through complementary mechanisms involving lipoxygenase products of DHA.

Published
2013
Full Text
View/download PDF

27. Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism

Author

Claude Genot, Constance Gayet, Marie-Caroline Michalski, Frédéric Fine, Florent Joffre, Jérome Bouvier, Jean-Luc Vendeuvre, Jean-Michel Chardigny, Ketsia Raynal-Ljutovac, Christelle Lopez, 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 de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), 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-Université Joseph Fourier - Grenoble 1 (UJF), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Nutrition, Centre National Interprofessionnel de l'Economie Laitière [Paris] (CNIEL), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Service transformation et valorisation des graines, Centre Technique Interprofessionnel des Oléagineux et du Chanvre (CETIOM), Technologie des Corps Gras et de la Nutrition Lipidique, Institut des Corps Gras (ITERG), Laboratoire D'analyses Industrielles, International Federation for Information Processing [Laxenburg, Austria] (IFIP), Actilait, Institut Technique du Lait et des Produits Laitiers, Unité de Nutrition Humaine (UNH), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), for the Steering Committee of RMT LISTRAL, 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 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, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, ACTIA (Association for Technical Coordination for Food Industry), Ministry of Agriculture, CNIEL (French dairy board), Poitou-Charentes region, 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 Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-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]), Terres Inovia, International Federation for Information Processing (IFIP), Vericel, Evelyne, 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: Triglycerides, 030309 nutrition & dietetics, Supramolecular chemistry, Solid-state, Biological Availability, 030209 endocrinology & metabolism, digestion, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, lipid, Animals, Humans, MESH: Animals, Triglycerides, MESH: Biological Availability, MESH: Lipid Metabolism, 2. Zero hunger, chemistry.chemical_classification, emulsion, 0303 health sciences, MESH: Humans, Chemistry, food, Fatty Acids, Fatty acid, Lipid metabolism, Cell Biology, Metabolism, Lipid Metabolism, Dietary Fats, Lipids, MESH: Lipids, Bioavailability, MESH: Fatty Acids, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Dietary Fats, Energy density, lipids (amino acids, peptides, and proteins), fatty acid, Digestion, metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

This review is respectfully dedicated to the memory of Michel Ollivon, Research Director at CNRS (Châtenay-Malabry, France), outstanding physico-chemist specialist of lipid organization, recipient of the Hilditch Memorial Lecture award, who was the initiator of the network RMT LISTRAL. We are also sadly paying tribute to Jean-Luc Vendeuvre, Food Engineer at the French Pork and Pig Institute (IFIP, Maisons-Alfort, France), outstanding expert in meat products who participated actively in RMT LISTRAL and provided unpublished data for figures in the present review, who passed away during review submission. RMT LISTRAL: Mixed Technological Network combining academic and industrial partners, devoted to the enhancement and divulgation of knowledge regarding structured dietary lipids.; International audience; On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen.

Published
2013
Full Text
View/download PDF

28. Low-dose food contaminants trigger sex-specific, hepatic metabolic changes in the progeny of obese mice

Author

Naville, Danielle, Pinteur, Claudie, Vega, Nathalie, Menade, Yoan, Vigier, Michèle, Le Bourdais, Alexandre, Labaronne, Emmanuel, Debard, Cyrille, Luquain-Costaz, Céline, Bégeot, Martine, Vidal, Hubert, Le Magueresse-Battistoni, Brigitte, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), 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)-Centre National de la Recherche Scientifique (CNRS)-Covalab, This work was supported by grants from Institut Benjamin Delessert (2010), Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail (ANSES, Programme National Environnement-Santé-Travail, EST-2010/2/2007), and The European Foundation of the Study Of Diabetes (EFSD/Novo Nordisk, program 2011). The authors declare no conflicts of interest., and Vericel, Evelyne

Subjects
DEHP, cholesterol, Estrogen sulfotransferase, BPA, MESH: Male, MESH: Tetrachlorodibenzodioxin, MESH: Body Weight, MESH: Polychlorinated Biphenyls, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Phenols, Persistent Organic Pollutant, MESH: Mice, Inbred C57BL, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Benzhydryl Compounds, MESH: Blotting, Western, MESH: Animals, biosynthesis, MESH: Female, MESH: Mice, MESH: Mice, Obese, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Liver
Abstract

International audience; Environmental contaminants are suspected to be involved in the epidemic incidence of metabolic disorders, food ingestion being a primarily route of exposure. We hypothesized that life-long consumption of a high-fat diet that contains low doses of pollutants will aggravate metabolic disorders induced by obesity itself. Mice were challenged from preconception throughout life with a high-fat diet containing pollutants commonly present in food (2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyl 153, diethylhexyl phthalate, and bisphenol A), added at low doses in the tolerable daily intake range. We measured several blood parameters, glucose and insulin tolerance, hepatic lipid accumulation, and gene expression in adult mice. Pollutant-exposed mice exhibited significant sex-dependent metabolic disorders in the absence of toxicity and weight gain. In males, pollutants increased the expression of hepatic genes (from 36 to 88%) encoding proteins related to cholesterol biosynthesis and decreased (40%) hepatic total cholesterol levels. In females, there was a marked deterioration of glucose tolerance, which may be related to the 2-fold induction of estrogen sulfotransferase and reduced expression of estrogen receptor α (25%) and estrogen target genes (>34%). Because of the very low doses of pollutants used in the mixture, these findings may have strong implications in terms of understanding the potential role of environmental contaminants in food in the development of metabolic diseases.

Published
2013
Full Text
View/download PDF

29. Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities

Author

Tarek Boussetta, Michel Guichardant, Michèle Fay, Fathi Driss, Jamel El-Benna, Michel Lagarde, Karama Makni-Maalej, Miao Liu, 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 de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-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), Vericel, Evelyne, 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
Lipopolysaccharides, Time Factors, Leukotriene B4, Neutrophils, Lipoxygenase, MESH: Neutrophils, MESH: Superoxides, Biochemistry, MESH: Dose-Response Relationship, Drug, chemistry.chemical_compound, 0302 clinical medicine, MESH: Peroxidase, Superoxides, Serine, Phosphorylation, MESH: NADPH Oxidase, chemistry.chemical_classification, 0303 health sciences, NADPH oxidase, biology, MESH: N-Formylmethionine Leucyl-Phenylalanine, MESH: Immunoblotting, Superoxide, MESH: Reactive Oxygen Species, N-Formylmethionine leucyl-phenylalanine, 3. Good health, Cell biology, N-Formylmethionine Leucyl-Phenylalanine, MESH: Docosahexaenoic Acids, 030220 oncology & carcinogenesis, Myeloperoxidase, Tetradecanoylphorbol Acetate, Human neutrophils, MESH: Cyclooxygenase 1, medicine.symptom, MESH: Cyclooxygenase 2, ROS-derived oxidative stress, protectin DX, Docosahexaenoic Acids, Immunoblotting, Inflammation, Article, 03 medical and health sciences, MESH: Cyclooxygenase Inhibitors, Isomerism, medicine, MESH: Isomerism, Humans, Cyclooxygenase Inhibitors, MESH: Serine, MESH: Tetradecanoylphorbol Acetate, MESH: Lipoxygenase, 030304 developmental biology, Peroxidase, Reactive oxygen species, MESH: Humans, MESH: Phosphorylation, Dose-Response Relationship, Drug, Organic Chemistry, MESH: Time Factors, NADPH Oxidases, Chemotaxis, Cell Biology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, inflammation, MESH: Prostaglandins, Cyclooxygenase 2, biology.protein, Cyclooxygenase 1, Prostaglandins, MESH: Lipopolysaccharides, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits in an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX)-a docosahexaenoic acid di-hydroxylated product which inhibits blood platelet aggregation-on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases.

Published
2013
Full Text
View/download PDF

30. Lipidomics of essential fatty acids and oxygenated metabolites

Author

Michel Lagarde, Nathalie Bernoud-Hubac, Michel Guichardant, Catherine Calzada, Evelyne Véricel, 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), Vericel, Evelyne, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
Leukotrienes, Peroxidation, Linoleic acid, Biological Availability, Biology, Prostanoids, Linoleic Acid, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lipidomics, Humans, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Arachidonic Acid, Fatty Acids, Essential, alpha-Linolenic acid, alpha-Linolenic Acid, Metabolism, Monooxygenase, Oxygen, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, Biochemistry, Fluxes, Fatty Acids, Unsaturated, Arachidonic acid, Lipid Peroxidation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Endocannabinoids, Food Science, Biotechnology, Polyunsaturated fatty acid
Abstract

International audience; Polyunsaturated fatty acids in mammals may be oxygenated into a myriad of bioactive products through di- and monooxygenases, products that are rapidly degraded to control their action. To evaluate the phenotypes of biological systems regarding this wide family of compounds, a lipidomics approach in function of time and compartments would be relevant. The current review takes into consideration most of the diverse oxygenated metabolites of essential fatty acids at large and their immediate degradation products. Their biological function and life span are considered. Overall, this is a fluxolipidomics approach that is emerging.

Published
2013
Full Text
View/download PDF

31. Bis(monoacylglycero)phosphate accumulation in macrophages induces intracellular cholesterol redistribution, attenuates liver-X receptor/ATP-Binding cassette transporter A1/ATP-binding cassette transporter G1 pathway, and impairs cholesterol efflux

Author

Daria Markina, Michel Lagarde, Asami Makino, Philippe Moulin, Shota Sakai, Etienne Lefai, Toshihide Kobayashi, Maud Arnal-Levron, Shizuya Yamashita, Isabelle Delton-Vandenbroucke, Céline Luquain-Costaz, Michel Guichardant, Vanessa Euthine, 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), Lipid Biology Laboratory, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine-Osaka University Graduate School of Medicine, This work was supported by grants from INSA-Lyon, Inserm, and RIKEN at Tokyo-Wako, 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), and Vericel, Evelyne

Subjects
MESH: Lipoproteins, LDL, Gene Expression, ATP-binding cassette transporter, chemistry.chemical_compound, Mice, 0302 clinical medicine, Homeostasis, MESH: Animals, Foam cell, ATP Binding Cassette Transporter, Subfamily G, Member 1, Liver X Receptors, 0303 health sciences, MESH: Lipoproteins, Orphan Nuclear Receptors, Plaque, Atherosclerotic, Cell biology, Lipoproteins, LDL, oxysterol receptors, Biochemistry, MESH: Orphan Nuclear Receptors, MESH: Homeostasis, MESH: ATP-Binding Cassette Transporters, Monoglycerides, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, MESH: Monoglycerides, Intracellular, MESH: Cholesterol, LDL, ATP Binding Cassette Transporter 1, MESH: Gene Expression, MESH: Foam Cells, Lipoproteins, Endosomes, Biology, Cholesterol 7 alpha-hydroxylase, Article, MESH: Lysophospholipids, Cell Line, 03 medical and health sciences, Animals, MESH: Plaque, Atherosclerotic, Liver X receptor, MESH: Mice, 030304 developmental biology, Cholesterol, Macrophages, MESH: Macrophages, Cholesterol, LDL, Sterol, MESH: Cell Line, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, MESH: Endosomes, ATP-Binding Cassette Transporters, atherosclerosis, Lysophospholipids, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Foam Cells
Abstract

Objective— Endosomal signature phospholipid bis(monoacylglycero)phosphate (BMP) has been involved in the regulation of cellular cholesterol homeostasis. Accumulation of BMP is a hallmark of lipid storage disorders and was recently reported as a noticeable feature of oxidized low-density lipoprotein–laden macrophages. This study was designed to delineate the consequences of macrophage BMP accumulation on intracellular cholesterol distribution, metabolism, and efflux and to unravel the underlying molecular mechanisms. Approach and Results— We have developed an experimental design to specifically increase BMP content in RAW 264.7 macrophages. After BMP accumulation, cell cholesterol distribution was markedly altered, despite no change in low-density lipoprotein uptake and hydrolysis, cholesterol esterification, or total cell cholesterol content. The expression of cholesterol-regulated genes sterol regulatory element–binding protein 2 and hydroxymethylglutaryl-coenzyme A reductase was decreased by 40%, indicative of an increase of endoplasmic reticulum–associated cholesterol. Cholesterol delivery to plasma membrane was reduced as evidenced by the 20% decrease of efflux by cyclodextrin. Functionally, BMP accumulation reduced cholesterol efflux to both apolipoprotein A1 and high-density lipoprotein by 40% and correlated with a 40% decrease in mRNA contents of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and liver-X receptor α and β. Foam cell formation induced by oxidized low-density lipoprotein exposure was exacerbated in BMP-enriched cells. Conclusions— The present work shows for the first time a strong functional link between BMP and cholesterol-regulating genes involved in both intracellular metabolism and efflux. We propose that accumulation of cellular BMP might contribute to the deregulation of cholesterol homeostasis in atheromatous macrophages.

Published
2013
Full Text
View/download PDF

32. White adipose tissue overproduces the lipid-mobilizing factor zinc α2-glycoprotein in chronic kidney disease

Author

Alain Géloën, Roxane E. Vella, Lionel Badet, Emilie Kalbacher, Christophe O. Soulage, Fitsum Guebre-Egziabher, Marine L. Croze, Caroline C. Pelletier, Laetitia Koppe, Denis Fouque, 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), 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), and Vericel, Evelyne

Subjects
Male, Biopsy, 030232 urology & nephrology, Adipose tissue, White adipose tissue, Mice, 0302 clinical medicine, Aged, 80 and over, 0303 health sciences, medicine.diagnostic_test, Middle Aged, Up-Regulation, 3. Good health, Nephrology, Lipogenesis, Female, zinc α2-glycoprotein, Peritoneal Dialysis, Adult, medicine.medical_specialty, Adipose Tissue, White, Adipokine, Biology, Article, 03 medical and health sciences, Adipokines, white adipose tissue, Renal Dialysis, 3T3-L1 Cells, Internal medicine, medicine, Animals, Humans, Lipolysis, Rats, Wistar, Renal Insufficiency, Chronic, lipogenesis, Aged, Glycoproteins, Uremia, 030304 developmental biology, medicine.disease, Rats, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, Endocrinology, ZAG, Case-Control Studies, lipolysis, Kidney Failure, Chronic, Carrier Proteins, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, chronic kidney disease, Kidney disease
Abstract

Chronic kidney disease (CKD) is frequently associated with protein energy wasting which has been recognized as a strong predictive factor of mortality. Zinc α2-glycoprotein (ZAG) has been proposed as a new adipokine involved in body weight control through its lipid mobilizing activity. We hypothesized that the uremic environment in CKD could alter ZAG production by white adipose tissue and contribute to CKD-associated metabolic disturbances. ZAG protein was quantified in 3T3-L1 adipocytes after incubation with plasma from healthy volunteers and CKD patients (20%, v/v). ZAG was also measured in white adipose tissue (WAT) from 5/6 nephrectomized rodents (Nx5/6) and subcutaneous adipose tissue biopsies from end-stage renal disease patients. Uremic plasma induced a significant increase in ZAG synthesis in 3T3-L1 adipocytes (+124%, p

Published
2013
Full Text
View/download PDF

33. Synthesis and Biological Interest of Structured Docosahexaenoic Acid-Containing Triacylglycerols and Phospholipids

Author

Michel Lagarde, Madeleine Picq, Nathalie Bernoud-Hubac, 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), The authors thank the support of Inserm, ANR, the French Ministry of Education and Research Education through INSA-Lyon, and a grant from the LISA Carnot institute, ProdInra, Migration, Vericel, Evelyne, 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), Mécanisme Moléculaire du Diabète (MMD), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm, ANR, French Ministry of Education and Research Education through INSA-Lyon, and LISA Carnot institute

Subjects
ENZYMATIC-SYNTHESIS, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], FISH OILS, Health benefits, CAPRYLIC-ACID, OXIDATIVE STABILITY, 03 medical and health sciences, chemistry.chemical_compound, Glycerol, Lipase, BRAIN, 030304 developmental biology, Nutrition, POLYUNSATURATED FATTY-ACIDS, 0303 health sciences, biology, LIPPROFILES, Chemistry, Organic Chemistry, food and beverages, CATALYZED REACTIONS, Lipids, 3. Good health, [SDV] Life Sciences [q-bio], DHA, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Biochemistry, Docosahexaenoic acid, Fat, biology.protein, RISK-FACTORS, lipids (amino acids, peptides, and proteins), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Abstract: In light of rapid progress in biochemistry and modern bioengineering, there is a great interest in understanding how modifying the structure of naturally occurring lipids can be used to improve their nutritional and health properties. Structured lipids (SLs) or custom-made lipids can supply functional fatty acids because of their specific positioning in the glycerol structure. Health benefits of n-3 fatty acids such as docosahexaenoic acid (DHA) have been widely reported. Little information is available on the potential for health benefits of the SLs molecules that are rich in DHA and have well defined structure.This review attempts to summarize our present state of knowledge of various approaches to produce structured DHA-containing triglycerides and phospholipids as well as their applications.

Published
2013
Full Text
View/download PDF

34. Inhibitory effects of in vivo oxidized high-density lipoproteins on platelet aggregation: evidence from patients with abetalipoproteinemia

Author

Calzada, Catherine, Véricel, Evelyne, Colas, Romain, Guillot, Nicolas, El Khoury, Graziella, Drai, Jocelyne, Sassolas, Agnès, Peretti, Noël, Ponsin, Gabriel, Lagarde, Michel, Moulin, Philippe, 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), Service de Nutrition et Gastroentérologie, Hospices Civils de Lyon (HCL), Fédération d'Endocrinologie, and Vericel, Evelyne

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, hydroxylated fatty acids, lipid peroxidation, vitamin E, metabolic disease, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; There is evidence that high-density lipoproteins (HDLs) may regulate platelet function, but disparate results exist regarding the effects of oxidized HDLs on platelets. The objective of our study was to determine the role of in vivo oxidized HDLs on platelet aggregation. Platelet aggregation and redox status were investigated in 5 patients with abetalipoproteinemia (ABLP) or homozygous hypobetalipoproteinemia, two rare metabolic diseases characterized by the absence of apolipoprotein B-containing lipoproteins, compared to 5 control subjects. Platelets isolated from plasma of patients with ABLP aggregated 4 to 10 times more than control platelets, depending on the agonist. By contrast, no differences in the extent of platelet aggregation were observed between ABLP platelet-rich plasma (PRP) and control PRP, suggesting the presence of a protective factor in ABLP plasma. ABLP HDLs inhibited agonist-induced platelet aggregation by binding to SR-BI, while control HDLs had no effect. On the other hand, lipoprotein-deficient plasma from patients with ABLP did not inhibit platelet aggregation. Severe oxidative stress was evidenced in patients with ABLP. Compared to control HDLs, ABLP HDLs showed a 40% decrease of α-tocopherol and an 11-fold increased malondialdehyde concentration. These results demonstrate that in vivo oxidized HDLs do not lose their antiaggregatory properties despite oxidation.-Calzada, C., Véricel, E., Colas, R., Guillot, N., El Khoury, G., Drai, J., Sassolas, A., Peretti, N., Ponsin, G., Lagarde, M., Moulin, P. Inhibitory effects of in vivo oxidized high-density lipoproteins on platelet aggregation: evidence from patients with abetalipoproteinemia.

Published
2013
Full Text
View/download PDF

35. Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: a randomized crossover clinical trial

Author

Vors, Cécile, Pineau, Gaëlle, Gabert, Laure, Drai, Jocelyne, Louche-Pélissier, Corinne, Defoort, Catherine, Lairon, Denis, Désage, Michel, Danthine, Sabine, Lambert-Porcheron, Stéphanie, Vidal, Hubert, Laville, Martine, Michalski, Marie-Caroline, 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)-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-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]), Service de Biochimie Générale, Métabolique et Moléculaire, Hospices Civils de Lyon (HCL), Laboratoire de Biochimie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gembloux Agro-Bio Tech [Gembloux], Université de Liège, This work was funded by the Centre National Interprofessionnel de l'Economie Laitière (CNIEL). CV received funding for PhD study by INRA and CNIEL. CV received a Research Prize from the Foundation Nestlé France. HV received financial support from Ezus-Lyon1. The funding agencies had no role in the data analysis., and Vericel, Evelyne

Subjects
MESH: Triglycerides, obesity, MESH: Hyperlipidemias, MESH: Intestinal Absorption, stable isotopes, MESH: Insulin, MESH: Carbon Dioxide, MESH: Cross-Over Studies, MESH: Body Mass Index, MESH: Fatty Acids, Omega-3, MESH: Meals, MESH: Obesity, MESH: Lipid Metabolism, MESH: Breakfast, emulsion, MESH: Fatty Acids, Nonesterified, MESH: Humans, MESH: Kinetics, intestinal absorption, chylomicron, MESH: Apolipoprotein B-48, MESH: Feces, MESH: Adult, MESH: Hunger, MESH: Male, MESH: Fatty Acids, MESH: Chylomicrons, MESH: Breath Tests, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Blood Glucose, MESH: Postprandial Period, MESH: Calorimetry, Indirect, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; BACKGROUND: Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward β-oxidation. OBJECTIVE: We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids. DESIGN: Nine normal-weight and 9 obese subjects were fed 40 g milk fat (+[(13)C]triacylglycerols), either emulsified or nonemulsified, in breakfasts of identical composition. We measured the postprandial triacylglycerol content and size of the chylomicron-rich fraction, plasma kinetics of [(13)C]fatty acids, exogenous lipid oxidation with breath-test/indirect calorimetry, and fecal excretion. RESULTS: The emulsified fat resulted in earlier (>1 h) and sharper chylomicron and [(13)C]fatty acid peaks in plasma than in spread fat in both groups (P < 0.0001). After 2 h, the emulsified fat resulted in greater apolipoprotein B-48 concentrations (9.7 ± 0.7 compared with 7.1 ± 0.9 mg/L; P < 0.05) in the normal-weight subjects than did the spread fat. In the obese subjects, emulsified fat resulted in a 3-fold greater chylomicron size (218 ± 24 nm) compared with the spread fat (P < 0.05). The emulsified fat induced higher dietary fatty acid spillover in plasma and a sharper (13)CO(2) appearance, which provoked increased exogenous lipid oxidation in each group: from 45% to 52% in normal-weight subjects (P < 0.05) and from 40% to 57% in obese subjects (P < 0.01). CONCLUSION: This study supports a new concept of "slow vs fast fat," whereby intestinal absorption can be modulated by structuring dietary fat to modulate postprandial lipemia and lipid β-oxidation in humans with different BMIs. This trial was registered at clinicaltrials.gov as NCT01249378.

Published
2013
Full Text
View/download PDF

36. Characterization and biological effects of di-hydroxylated compounds deriving from the lipoxygenation of ALA.: Di-hydroxylated metabolites from ALA

Author

Liu, Miao, Chen, Ping, Véricel, Evelyne, Lelli, Moreno, Beguin, Laetitia, Lagarde, Michel, Guichardant, Michel, Vericel, Evelyne, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tea Science Department, College of Agriculture and Biotechnology, College of Agriculture and Biotechnology, Zhejiang University-Zhejiang University, ISA - Centre de RMN à très hauts champs, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and This study was supported by Inserm and the French Ministry of Education and Research. Miao Liu is a Ph.D. student granted from the China Scholarship Council.

Subjects
MESH: Humans, MESH: alpha-Linolenic Acid, MESH: Hydroxylation, MESH: Molecular Structure, MESH: Anti-Inflammatory Agents, Non-Steroidal, MESH: Recombinant Proteins, platelet aggrgation, octadecatrienoic acid, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Structure-Activity Relationship, MESH: Arachidonate 15-Lipoxygenase, anti-inflammatory activity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Blood Platelets, 15 lipoxygenase
Abstract

International audience; We have recently described a di-hydroxylated compound called protectin DX (PDX) which derives from docosahexaenoic acid (DHA) by double lipoxygenation. PDX exhibits anti-aggregatory and anti-inflammatory properties, that are also exhibited by similar molecules, called poxytrins, which possess the same E,Z,E conjugated triene geometry, and are synthesized from other polyunsaturated fatty acids with 22 or 20 carbons. Here we present new biological activities of di-hydroxylated metabolites deriving from α-linolenic acid (18:3n-3) treated by soybean 15-lipoxygenase (sLOX). We show that 18:3n-3 is converted by sLOX into mainly 13(S)-OH-18:3 after reduction of the hydroperoxide product. But surprisingly, and in contrast to DHA which is metabolized into only one di-hydroxylated compound, 18:3n-3 leads to four di-hydroxylated fatty acid isomers. We report here the complete characterization of these compounds using high field NMR and GC-MS techniques, and some of their biological activities. These compounds are: 9(R),16(S)-dihydroxy-10E,12E,14E-octadecatrienoic acid, 9(S),16(S)-dihydroxy-10E,12E,14E-octadecatrienoic acid, 9(S),16(S)-dihydroxy-10E,12Z,14E-octadecatrienoic acid, and 9(R),16(S)-dihydroxy-10E,12Z,14E-octadecatrienoic acid. They can also be synthesized by the human recombinant 15-lipoxygenase (type 2). Their inhibitory effect on blood platelet and anti-inflammatory properties were compared with those already reported for PDX.

Published
2013
Full Text
View/download PDF

37. Chronic treatment with myo-inositol reduces white adipose tissue accretion and improves insulin sensitivity in female mice.: Metabolic effects of myo-inositol

Author

Croze, Marine, Vella, Roxane, Pillon, Nicolas, Soula, Hédi, Hadji, Lilas, Guichardant, Michel, Soulage, Christophe, Vericel, Evelyne, 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), and This work was supported by INSERM and INSA-Lyon. M.L. CROZE, R.E. VELLA and L. HADJI were recipient for grants from the French 'Ministère de la Recherche et de la Technologie'.

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, myo-inositol, antioxidant, skeletal muscle: white adipose tissue, fat mas, insulin-sensitizing, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Type 2 diabetes is a complex disease characterized by a state of insulin resistance in peripheral tissues such as skeletal muscle, adipose tissue or liver. Some inositol isomers have been reported to possess insulin-mimetic activity and to be efficient in lowering blood glucose level. The aim of the present study was to assess in mice the metabolic effects of a chronic treatment with myo-inositol, the most common stereoisomer of inositol. Mice given myo-inositol treatment (0.9 or 1.2 mg g(-1) day(-1), 15 days, orally or intraperitoneally) exhibited an improved glucose tolerance due to a greater insulin sensitivity. Mice treated with myo-inositol exhibited a decreased white adipose tissue accretion (-33%, P

Published
2013
Full Text
View/download PDF

38. p-Cresyl sulfate promotes insulin resistance associated with CKD

Author

Laetitia Koppe, Raymond Vanholder, Christophe O. Soulage, Caroline C. Pelletier, Ziad A. Massy, Stéphane Chambert, Roxane E. Vella, Yann Dugenet, Nicolas J. Pillon, Hédi Soula, Denis Fouque, Marine L. Croze, Griet Glorieux, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 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), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), CHU Amiens-Picardie, Nephrology Section [Ghent], Ghent University Hospital, 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), 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 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), Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Witaxos DF3 SAS/BioActor b.v. BioPartner Center, This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM) and Institut National des Sciences Appliquées de Lyon (INSA-Lyon). L. Koppe held a fellowship from 'Fondation pour la Recherche Médicale' and. C.Pelletier held a grant from 'Société Française de Néphrologie'. N.J. Pillon, M.L. Croze and R.E. Vella were supported by grants from the French Ministère de lʼEducation Nationale, de la Recherche et de la Technologie., Vericel, Evelyne, Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), 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
MESH: Signal Transduction, medicine.medical_treatment, 030232 urology & nephrology, Adipose tissue, Cresols, Mice, 0302 clinical medicine, Adipocytes, Insulin, MESH: Uremia, MESH: Animals, Extracellular Signal-Regulated MAP Kinases, MESH: Extracellular Signal-Regulated MAP Kinases, MESH: Lipid Metabolism, 0303 health sciences, MESH: Muscle, Skeletal, biology, MESH: Hypercholesterolemia, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], humanities, 3. Good health, MESH: Glucose, MESH: Insulin Resistance, MESH: Cresols, MESH: Adipose Tissue, White, Nephrology, Signal Transduction, medicine.medical_specialty, Adipose Tissue, White, Hypercholesterolemia, MESH: Renal Insufficiency, Chronic, MESH: Insulin, Sulfuric Acid Esters, Carbohydrate metabolism, 03 medical and health sciences, Insulin resistance, MESH: Mice, Inbred C57BL, Internal medicine, Diabetes mellitus, medicine, Animals, Renal Insufficiency, Chronic, Muscle, Skeletal, MESH: Mice, Pancreatic hormone, MESH: Adipocytes, Uremia, 030304 developmental biology, business.industry, Lipid Metabolism, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Insulin receptor, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Prebiotics, Glucose, Prebiotics, Basic Research, Endocrinology, Hyperglycemia, biology.protein, Insulin Resistance, MESH: Disease Models, Animal, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Hyperglycemia, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Dyslipidemia
Abstract

International audience; The mechanisms underlying the insulin resistance that frequently accompanies CKD are poorly understood, but the retention of renally excreted compounds may play a role. One such compound is p-cresyl sulfate (PCS), a protein-bound uremic toxin that originates from tyrosine metabolism by intestinal microbes. Here, we sought to determine whether PCS contributes to CKD-associated insulin resistance. Administering PCS to mice with normal kidney function for 4 weeks triggered insulin resistance, loss of fat mass, and ectopic redistribution of lipid in muscle and liver, mimicking features associated with CKD. Mice treated with PCS exhibited altered insulin signaling in skeletal muscle through ERK1/2 activation. In addition, exposing C2C12 myotubes to concentrations of PCS observed in CKD caused insulin resistance through direct activation of ERK1/2. Subtotal nephrectomy led to insulin resistance and dyslipidemia in mice, and treatment with the prebiotic arabino-xylo-oligosaccharide, which reduced serum PCS by decreasing intestinal production of p-cresol, prevented these metabolic derangements. Taken together, these data suggest that PCS contributes to insulin resistance and that targeting PCS may be a therapeutic strategy in CKD.

Published
2013
Full Text
View/download PDF

39. Gene network analysis leads to functional validation of pathways linked to cancer cell growth and survival

Author

Emmanuelle Berger, Alain Géloën, Hubert Vidal, Nathalie Vega, 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), 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), and Vericel, Evelyne

Subjects
MESH: Signal Transduction, Gene regulatory network, Bioinformatics, Applied Microbiology and Biotechnology, 0302 clinical medicine, MESH: Liver Neoplasms, human hepatocellular carcinoma, CEBPA, Cluster Analysis, Gene Regulatory Networks, MESH: Carcinoma, Hepatocellular, Oligonucleotide Array Sequence Analysis, MESH: Gene Regulatory Networks, 0303 health sciences, MESH: Real-Time Polymerase Chain Reaction, Liver Neoplasms, General Medicine, Hep G2 Cells, MESH: Gene Expression Regulation, Neoplastic, MESH: Transcription Factors, 3. Good health, Gene Expression Regulation, Neoplastic, Liver, MESH: Cell Survival, 030220 oncology & carcinogenesis, MESH: Cell Growth Processes, Molecular Medicine, Signal transduction, signal transduction, MESH: Computational Biology, Cell signaling, Carcinoma, Hepatocellular, MESH: Cell Line, Tumor, Cell Survival, MAP Kinase Signaling System, In silico, MESH: Hep G2 Cells, Cell Growth Processes, Biology, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, MESH: Gene Expression Profiling, Cell Line, Tumor, Humans, RNA, Messenger, Transcription factor, 030304 developmental biology, MESH: RNA, Messenger, real-time proliferation assay, MESH: Humans, MESH: MAP Kinase Signaling System, Gene Expression Profiling, MESH: Transcriptome, Computational Biology, MESH: Cluster Analysis, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cancer cell, MESH: Oligonucleotide Array Sequence Analysis, FOXM1, Cancer research, Transcriptome, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Transcription Factors, MESH: Liver
Abstract

International audience; Hepatocellular carcinoma (HCC) represents one of the most frequently diagnosed human cancers; however, there are currently few treatment alternatives to surgical resection. In this study we performed bioinformatic analysis of previously published transcriptomic data in order to characterize liver specific networks, including biological functions, signaling pathways and transcription factors, potentially dysregulated in HCC. By incorporating specific signaling inhibitors into real-time proliferation assays using HepG2 cells, we then validated these in silico results. We found that G protein subunits Gi/G0, protein kinase C, Mek1/2, and Erk1/2 (P42/44), JAK1, PPARA and NFκB p65 subunit were the major signaling molecules required for survival and proliferation of human HCC cell lines. We also found that these pathways regulate the expression of key hepatic transcription factors involved in cell differentiation, such as CEBPA, EGR1, FOXM1 and PPARs. By combining bioinformatic and functional analyses, major signaling pathways related to tumorigenicity in HCC are revealed, thereby elucidating potential targets for drug therapies.

Published
2012
Full Text
View/download PDF

40. Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia

Author

Di Filippo, Mathilde, Créhalet, Hervé, Samson-Bouma, Marie Elisabeth, Bonnet, Véronique, Aggerbeck, Lawrence, Rabès, Jean-Pierre, Gottrand, Frederic, Luc, Gérald, Bozon, Dominique, Sassolas, Agnès, Service de Biochimie et Biologie Moléculaire, Hospices Civils de Lyon (HCL)-Centre de Biologie et de pathologie Est, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacologie, toxicologie et signalisation cellulaire (U747), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de Médecine Interne, PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Vericel, Evelyne

Subjects
MESH: Humans, MESH: Mutation, MESH: Child, Preschool, MESH: Genetic Predisposition to Disease, MESH: Abetalipoproteinemia, MESH: Carrier Proteins, genotype-phenotype correlation, familial hypocholesterolemia, functional analysis, splicing, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, hepatosteatosis, gene expression, lipoprotein/assembly, chylomicrons, genetics, MESH: DNA Mutational Analysis, dyslipidemias, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Abetalipoproteinemia (ABL) is an inherited disease characterized by the defective assembly and secretion of apolipoprotein B-containing lipoproteins caused by mutations in the microsomal triglyceride transfer protein large subunit (MTP) gene (MTTP). We report here a female patient with an unusual clinical and biochemical ABL phenotype. She presented with severe liver injury, low levels of LDL-cholesterol, and subnormal levels of vitamin E, but only mild fat malabsorption and no retinitis pigmentosa or acanthocytosis. Our objective was to search for MTTP mutations and to determine the relationship between the genotype and this particular phenotype. The subject exhibited compound heterozygosity for two novel MTTP mutations: one missense mutation (p.Leu435His) and an intronic deletion (c.619-5_619-2del). COS-1 cells expressing the missense mutant protein exhibited negligible levels of MTP activity. In contrast, the minigene splicing reporter assay showed an incomplete splicing defect of the intronic deletion, with 26% of the normal splicing being maintained in the transfected HeLa cells. The small amount of MTP activity resulting from the residual normal splicing in the patient explains the atypical phenotype observed. Our investigation provides an example of a functional analysis of unclassified variations, which is an absolute necessity for the molecular diagnosis of atypical ABL cases.

Published
2012
Full Text
View/download PDF

41. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Author

Awada, Manar, Soulage, Christophe, Meynier, Anne, Debard, Cyrille, Plaisancié, Pascale, Benoit, Bérengère, Picard, Grégoire, Loizon, Emmanuelle, Chauvin, Marie-Agnès, Estienne, Monique, Peretti, Noël, Guichardant, Michel, Lagarde, Michel, Genot, Claude, Michalski, Marie-Caroline, Vericel, Evelyne, 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), 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), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), and Institut National de la Recherche Agronomique (INRA)

Subjects
4-hydroxy-2-alkenals, MESH: Inflammation, MESH: Oxidation-Reduction, MESH: Intestinal Absorption, MESH: Heat-Shock Proteins, MESH: Lipid Peroxidation, MESH: Fatty Acids, Omega-3, MESH: Mice, Inbred C57BL, MESH: Animals, intestine, MESH: Mice, Nutrition, MESH: Humans, MESH: Oxidative Stress, MESH: Biological Markers, lipid peroxidation, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Diet, High-Fat, MESH: Glutathione Peroxidase, MESH: Aldehydes, MESH: Caco-2 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, polyunsaturated fatty acids, MESH: Intestines
Abstract

ISI Document Delivery No.: 004QQTimes Cited: 0Cited Reference Count: 46Cited References: Pillon Nicolas J., 2011, CHEMICAL RESEARCH IN TOXICOLOGY, V24, P752Awada, Manar Soulage, Christophe O. Meynier, Anne Debard, Cyrille Plaisancie, Pascale Benoit, Berengere Picard, Gregory Loizon, Emmanuelle Chauvin, Marie-Agnes Estienne, Monique Peretti, Noel Guichardant, Michel Lagarde, Michel Genot, Claude Michalski, Marie-CarolineFrench National Research Agency (ANR)[ANR-08-ALIA-002]; ANRThis work was supported by the French National Research Agency (ANR) Grant ANR-08-ALIA-002, AGECANINOX project.M. Awada acknowledges her PhD grant from ANR. The authors thank Lucie Ribourg and Michele Viau for their work on oil mixtures. Patricia Daira is acknowledged for her help with the 4-hydroxy-2-alkenal assay. The authors thank Jean-Michel Chardigny for useful discussions. Isabelle Jouanin (Plateforme AXIOM-MetaToul, Toulouse) is acknowledged for the synthesis of internal standards to measure 4-hydroxyl-2-alkenals in fat. Yvonne Masson is acknowledged for revising the English-language manuscript.Amer soc biochemistry molecular biology incBethesda[Awada, Manar; Plaisancie, Pascale; Estienne, Monique; Michalski, Marie-Caroline] INRA, CarMeN Lab U1235, F-69621 Villeurbanne, France. [Awada, Manar; Soulage, Christophe O.; Guichardant, Michel; Lagarde, Michel; Michalski, Marie-Caroline] Inst Natl Sci Appl, IMBL, F-69621 Villeurbanne, France. [Meynier, Anne; Genot, Claude] INRA, Biopolymeres Interact Assemblages UR1268, F-44300 Nantes, France. [Debard, Cyrille; Chauvin, Marie-Agnes] INSERM, U1060, CarMeN Lab, F-69921 Oullins, France. [Benoit, Berengere; Picard, Gregory; Loizon, Emmanuelle; Peretti, Noel; Michalski, Marie-Caroline] Univ Lyon 1, F-69622 Villeurbanne, France.marie-caroline.michalski@insa-lyon.fr; International audience; Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to -19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine.

Published
2012
Full Text
View/download PDF

42. SREBP-1 transcription factors regulate skeletal muscle cell size by controlling protein synthesis through myogenic regulatory factors

Author

Etienne Lefai, Chantal Simon, Sophie Rome, Stéphanie Chanon, Georges Némoz, Kevin Dessalle, Isao Fujii, Vanessa Euthine, Joffrey Delarichaudy, Hubert Vidal, Vericel, Evelyne, 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), Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences-Sojo University, This work was supported by INSERM, INRA, and a grant from the Cance'ropoˆle Lyon Rhoˆne-Alpes (Procan Axe III 2010). KD and JDL are recipients of PhD fellowships from the French Ministry of Higher Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
Anatomy and Physiology, Muscle Fibers, Skeletal, Gene Expression, lcsh:Medicine, Biochemistry, 0302 clinical medicine, Molecular Cell Biology, Homeostasis, RNA, Small Interfering, lcsh:Science, Musculoskeletal System, 0303 health sciences, Multidisciplinary, Myogenesis, MEF2 Transcription Factors, Muscle Biochemistry, Muscle atrophy, Cell biology, medicine.anatomical_structure, Myogenic Regulatory Factors, Muscle, Medicine, Myogenin, lipids (amino acids, peptides, and proteins), medicine.symptom, Cellular Types, Sterol Regulatory Element Binding Protein 1, Research Article, Signal Transduction, Sarcomeres, Cell Physiology, MADS Domain Proteins, Biology, Muscle Types, 03 medical and health sciences, MyoD Protein, DNA-binding proteins, medicine, Humans, Muscle, Skeletal, Transcription factor, 030304 developmental biology, Cell Size, Muscle Cells, lcsh:R, Skeletal muscle, Proteins, Sterol regulatory element-binding protein, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Protein Biosynthesis, Myogenic regulatory factors, Proteolysis, lcsh:Q, Physiological Processes, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

International audience; SREBP-1 are ubiquitously expressed transcription factors, strongly expressed in lipogenic tissues where they regulate several metabolic processes like fatty acid synthesis. In skeletal muscle, SREBP-1 proteins regulate the expression of hundreds of genes, and we previously showed that their overexpression induced muscle atrophy together with a combined lack of expression of myogenic regulatory factors. Here we present evidences that SREBP-1 regulate muscle protein synthesis through the downregulation of the expression of MYOD1, MYOG and MEF2C factors. In myotubes overexpressing SREBP-1, restoring the expression of myogenic factors prevented atrophy and rescued protein synthesis, without affecting SREBP-1 action on atrogenes and proteolysis. Our results point out the roles of MRFs in the maintenance of the protein content and cell size in adult muscle fibre, and contribute to decipher the mechanisms by which SREBP-1 regulate muscle mass.

Published
2012
Full Text
View/download PDF

43. Gender differences in transcriptional signature of developing rat testes and ovaries following embryonic exposure to 2,3,7,8-TCDD

Author

Solange Magre, Diane Rebourcet, Brigitte Le Magueresse-Battistoni, Emmanuelle Meugnier, Muhammad Ishaq, Hubert Vidal, Cyrille Debard, Richard Wargnier, Joëlle Cohen-Tannoudji, 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), 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), This research project was supported by Agence Nationale pour la Recherche (ANR-06-PNRA-006-01, Dhyoxhyme project) and by Agence franc¸aise de se'curite' sanitaire de l'environnement et du travail (AFSSET, EST-2006/1/33). DR is the recipient of subsides from ANR (ANR-06-PNRA-006-01) and Schering-Plough (FARO-grant-0119-10/Organon). RW is the recipient of subsides from ANR (ANR-CES-2008-011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-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 Paris Diderot - Paris 7 (UPD7), 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), 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, Polychlorinated Dibenzodioxins, Transcription, Genetic, Microarrays, Toxicology, MESH: Reproduction, Transcriptomes, Rats, Sprague-Dawley, Endocrinology, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, MESH: Pituitary Gland, MESH: Animals, heterocyclic compounds, GROWTH-FACTORS, NULL MUTATION, lcsh:Science, Oligonucleotide Array Sequence Analysis, GENE-EXPRESSION, Regulation of gene expression, 0303 health sciences, Reproduction, Genomics, MESH: Transcription Factors, In utero, Pituitary Gland, Prenatal Exposure Delayed Effects, Medicine, 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD, MESH: Sex Characteristics, ARYL-HYDROCARBON RECEPTOR, medicine.medical_specialty, endocrine system, Offspring, Toxic Agents, Endocrine System, MESH: Prenatal Exposure Delayed Effects, MESH: Gene Expression Profiling, 03 medical and health sciences, FEMALE RATS, MESH: Promoter Regions, Genetic, Reproductive Endocrinology, Endocrine system, SEMINAL-VESICLE, Biology, Crosses, Genetic, Microarray analysis techniques, lcsh:R, Reproductive System, Computational Biology, Aryl hydrocarbon receptor, lcsh:Q, MESH: Female, Software, 030217 neurology & neurosurgery, Transcription Factors, MESH: Liver, Anatomy and Physiology, Gene Expression, lcsh:Medicine, MESH: Rats, Sprague-Dawley, MESH: Animals, Newborn, Reproductive Physiology, Testis, Molecular Cell Biology, MESH: Gene Expression Regulation, Developmental, Promoter Regions, Genetic, Sex Characteristics, Multidisciplinary, biology, MESH: Testis, Gene Expression Regulation, Developmental, Embryo, MESH: Chemokines, MESH: Crosses, Genetic, Liver, Female, Chemokines, Research Article, MESH: Ovary, MESH: Rats, IN-UTERO, DIOXIN, MICE, MESH: Software, Genome Analysis Tools, Internal medicine, medicine, Animals, 030304 developmental biology, Endocrine Physiology, Gene Expression Profiling, MESH: Transcription, Genetic, Ovary, MESH: Embryo, Mammalian, Embryo, Mammalian, MESH: Male, Rats, MESH: Tetrachlorodibenzodioxin, Gene expression profiling, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Animals, Newborn, MESH: Oligonucleotide Array Sequence Analysis, biology.protein, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Dioxins are persistent organic pollutants interfering with endocrine systems and causing reproductive and developmental disorders. The objective of our project was to determine the impact of an in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive function of male and female offspring in the rat with a special emphasis on the immature period. We used a low dose of TCDD (unique exposure by oral gavage of 200 ng/kg at 15.5 days of gestation) in order to mirror a response to an environmental dose of TCDD not altering fertility of the progeny. We choose a global gene expression approach using Affymetrix microarray analysis, and testes of 5 days and ovaries of 14 days of age. Less than 1% of the expressed genes in gonads were altered following embryonic TCDD exposure; specifically, 113 genes in ovaries and 56 in testes with 7 genes common to both sex gonads. It included the repressor of the aryl hydrocarbon receptor (Ahrr), the chemokines Ccl5 and Cxcl4 previously shown to be regulated by dioxin in testis, Pgds2/Hpgds and 3 others uncharacterized. To validate and extend the microarray data we realized real-time PCR on gonads at various developmental periods of interest (from 3 to 25 days for ovaries, from 5 to the adult age for testes). Overall, our results evidenced that both sex gonads responded differently to TCDD exposure. For example, we observed induction of the canonic battery of TCDD-induced genes coding enzymes of the detoxifying machinery in ovaries aged of 3-14 days of age (except Cyp1a1 induced at 3-10 days) but not in testes of 5 days (except Ahrr). We also illustrated that inflammatory pathway is one pathway activated by TCDD in gonads. Finally, we identified several new genes targeted by TCDD including Fgf13 in testis and one gene, Ptgds2/Hpgds regulated in the two sex gonads.

Published
2012
Full Text
View/download PDF

44. Reduction of endoplasmic reticulum stress using chemical chaperones or Grp78 overexpression does not protect muscle cells from palmitate-induced insulin resistance

Author

Rieusset, Jennifer, Chauvin, Marie-Agnès, Durand, Annie, Bravard, Amélie, Laugerette, Fabienne, Michalski, Marie-Caroline, Vidal, Hubert, Vericel, Evelyne, 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
MESH: Tunicamycin, MESH: Muscle Fibers, Skeletal, MESH: Insulin, MESH: Heat-Shock Proteins, MESH: Palmitates, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Insulin Resistance, MESH: Diet, MESH: Mice, Inbred C57BL, MESH: Dietary Fats, MESH: Endoplasmic Reticulum Stress, MESH: Butylamines, MESH: Taurochenodeoxycholic Acid, MESH: Animals, MESH: Mice, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Endoplasmic reticulum (ER) stress is proposed as a novel link between elevated fatty acids levels, obesity and insulin resistance in liver and adipose tissue. However, it is unknown whether ER stress also contributes to lipid-induced insulin resistance in skeletal muscle, the major tissue responsible of insulin-stimulated glucose disposal. Here, we investigated the possible role of ER stress in palmitate-induced alterations of insulin action, both in vivo, in gastrocnemius of high-palm diet fed mice, and in vitro, in palmitate-treated C(2)C(12) myotubes. We demonstrated that 8 weeks of high-palm diet increased the expression of ER stress markers in muscle of mice, whereas ex-vivo insulin-stimulated PKB phosphorylation was not altered in this tissue. In addition, exposure of C(2)C(12) myotubes to either tuncamycine or palmitate induced ER stress and altered insulin-stimulated PKB phosphorylation. However, alleviation of ER stress by either TUDCA or 4-PBA treatments, or by overexpressing Grp78, did not restore palmitate-induced reduction of insulin-stimulated PKB phosphorylation in C(2)C(12) myotubes. This work highlights that, even ER stress is associated with palmitate-induced alterations of insulin signaling, ER stress is likely not the major culprit of this effect in myotubes, suggesting that the previously proposed link between ER stress and insulin resistance is less important in skeletal muscle than in adipose tissue and liver.

Published
2012
Full Text
View/download PDF

45. Functional lipidomics of oxidized products from polyunsaturated fatty acids

Author

Ping Chen, Catherine Calzada, Michel Lagarde, Romain A. Colas, Evelyne Véricel, Michel Guichardant, Miao Liu, 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), The support of INSERM, Ministry of Education and Research, and LISA Carnot Institute is acknowledged., 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), and Vericel, Evelyne

Subjects
MESH: Oxidation-Reduction, Oxygenase, Lipid peroxidation, Lipid mediators, medicine.disease_cause, Biochemistry, Dioxygenases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MESH: Dioxygenases, Lipidomics, medicine, Organic chemistry, Animals, Humans, MESH: Animals, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Degree of unsaturation, MESH: Humans, Organic Chemistry, Computational Biology, Cell Biology, Lipid signaling, MESH: Fatty Acids, Unsaturated, Monooxygenase, Lipid analysis, Oxygen, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, Fatty Acids, Unsaturated, Oxygenases, Oxidation-Reduction, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Oxidative stress, MESH: Oxygen, Polyunsaturated fatty acid, MESH: Computational Biology
Abstract

International audience; Because of their high degree of unsaturation, polyunsaturated fatty acids (PUFA) in mammals, with mainly 18, 20 and 22 carbons, can easily be autooxidized, and converted into many oxidized derivatives and degradation products. This short review reports on some of those relevant to the evaluation of oxidative stress in situ. In addition, the enzyme-dependent oxygenation by both dioxygenases and monooxygenases is briefly reviewed by functional and/or metabolic categories, pointing out the structure variety and the analytical approaches.

Published
2011
Full Text
View/download PDF

46. Phospholipase D regulates myogenic differentiation through the activation of both mTORC1 and mTORC2 complexes

Author

Jaafar, Rami, Zeiller, Caroline, Pirola, Luciano, Di Grazia, Antonio, Naro, Fabio, Vidal, Hubert, Lefai, Etienne, Nemoz, Georges, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Istologia ed Embriologia Medica, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-Istituto Interuniversitario di Miologia, This work has been supported by a grant from the Association Française contre les Myopathies (MNM2 2007), and a fellowship to R.J. from the Association pour la Recherche sur le Cancer., and Vericel, Evelyne

Subjects
MESH: Cell Differentiation, MESH: Enzyme Activation, MESH: Rats, P70 S6 KINASE, macromolecular substances, MESH: Arginine Vasopressin, DEPENDENT MANNER, MESH: Animals, MESH: Myoblasts, MESH: Mice, MESH: TOR Serine-Threonine Kinases, PHOSPHATIDIC-ACID, MESH: Ribosomal Protein S6 Kinases, MESH: Proto-Oncogene Proteins c-akt, SKELETAL-MUSCLE REGENERATION, ACTIN CYTOSKELETON, PROTEIN-KINASE, C2C12 MYOGENESIS, enzymes and coenzymes (carbohydrates), [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MAMMALIAN TARGET, MESH: Phospholipase D, MESH: Muscle Development, lipids (amino acids, peptides, and proteins), biological phenomena, cell phenomena, and immunity, MYOBLAST DIFFERENTIATION, SUBCELLULAR-LOCALIZATION, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; How phospholipase D (PLD) is involved in myogenesis remains unclear. At the onset of myogenic differentiation of L6 cells induced by the PLD agonist vasopressin in the absence of serum, mTORC1 complex was rapidly activated, as reflected by phosphorylation of S6 kinase1 (S6K1). Both the long (p85) and short (p70) S6K1 isoforms were phosphorylated in a PLD1-dependent way. Short rapamycin treatment specifically inhibiting mTORC1 suppressed p70 but not p85 phosphorylation, suggesting that p85 might be directly activated by phosphatidic acid. Vasopressin stimulation also induced phosphorylation of Akt on Ser-473 through PLD1-dependent activation of mTORC2 complex. In this model of myogenesis, mTORC2 had a positive role mostly unrelated to Akt activation, whereas mTORC1 had a negative role, associated with S6K1-induced Rictor phosphorylation. The PLD requirement for differentiation can thus be attributed to its ability to trigger via mTORC2 activation the phosphorylation of an effector that could be PKCα. Moreover, PLD is involved in a counter-regulation loop expected to limit the response. This study thus brings new insights in the intricate way PLD and mTOR cooperate to control myogenesis.

Published
2011
Full Text
View/download PDF

47. 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
Full Text
View/download PDF

48. 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
Full Text
View/download PDF

49. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

Author

Chen, Ping, Véricel, Evelyne, Lagarde, Michel, Guichardant, Michel, 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), INSERM, Ministry of Education and Research, Lipides pour l'Industrie et la Sante (LISA) Carnot Institute, Chinese Educational Council, and Vericel, Evelyne

Subjects
MESH: Humans, MESH: Prostaglandin-Endoperoxide Synthases, MESH: Thromboxanes, MESH: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, MESH: Fatty Acids, Unsaturated, docosahexaenoic acid, docosatrienes, MESH: Arachidonic Acid, MESH: Receptors, Thromboxane, MESH: Cyclooxygenase Inhibitors, MESH: Docosahexaenoic Acids, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Dicarboxylic Acids, 15-lipoxygenase, platelet aggregation, MESH: Platelet Aggregation Inhibitors, MESH: Collagen, MESH: Isomerism, thromboxane receptor, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Oxygen, MESH: Blood Platelets, MESH: Cyclic AMP, MESH: Platelet Aggregation
Abstract

International audience; Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown. Isomers of protectin D1 were synthesized using soybean lipoxygenase and tested for their ability to inhibit human blood platelet aggregation. A geometric isomer called PDX, previously described with the 11E,13Z,15E geometry, instead of 11E,13E,15Z in PD1, inhibited platelet aggregation at submicromolar concentrations when induced by either collagen, arachidonic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and thromboxane receptor site. Interestingly, all the metabolites tested exhibiting the E,Z,E-conjugated triene were active, whereas E,E,Z trienes (as in PD1) or all-trans (E,E,E) trienes were inactive. We conclude that PDX and other oxygenated products from PUFAs of nutritional interest, having the E,Z,E-conjugated triene motif and collectively named poxytrins (PUFA oxygenated trienes), might have antithrombotic potential.

Published
2011
Full Text
View/download PDF

50. Direct and indirect impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on adult mouse Leydig cells: an in vitro study

Author

Naville, Danielle, Rebourcet, Diane, Chauvin, Marie-Agnès, Vega, Nathalie, Jalabert, Audrey, Vigier, Michèle, Loizon, Emmanuelle, Bégeot, Martine, Le Magueresse-Battistoni, Brigitte, Vericel, Evelyne, 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This work was supported by Inserm (Institut National de la Santé et de 308 la Recherche Médicale), INRA (Institut National de la Recherche Agronomique), University 309 of Lyon 1 and specific grants from AFSSET (EST-2006/1/33) and ANR (ANR-06-PNRA- 310 006-01). DR was funded by ANR (ANR-06-PNRA-006-01) and Schering-Plough (FARO 311 Organon).

Subjects
endocrine system, MESH: Gene Expression, MESH: Testosterone, MESH: Leydig Cells, MESH: Aryl Hydrocarbon Hydroxylases, Leydig cell, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Platelet Factor 4, MESH: Basic Helix-Loop-Helix Transcription Factors, MESH: Chemokine CCL5, heterocyclic compounds, MESH: Animals, MESH: Mice, reproductive and urinary physiology, Dioxin, AhR, chemokine, in vitro, MESH: Male, MESH: Tetrachlorodibenzodioxin, stomatognathic diseases, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Repressor Proteins, MESH: Receptors, Aryl Hydrocarbon, MESH: Tumor Necrosis Factor-alpha, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Cells, Cultured
Abstract

International audience; 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are ubiquitous environmental pollutants that exert adverse effects on reproductive processes. In testis, Leydig cells which produce testosterone are under hormonal and local control exerted by cytokines including TNFα. Using mouse Leydig primary cell cultures as a model, we studied the effects of TCDD on the steroidogenic outcome of Leydig cells and the gene expression levels of Ccl5 and Cxcl4, previously shown to be target genes of TCDD in testis. We found that TCDD did not alter the steroidogenic outcome of Leydig cells but that it up-regulated Cxcl4 gene expression levels. TCDD also impacted Ccl5 gene expression when cells had been co-treated with TNFα. TCDD action probably initiated with binding to the aryl hydrocarbon receptor (AhR) present on Leydig cells. TCDD regulated the gene expression levels of AhR (transient down-regulation) and its repressor AhRR and Cyp1b1 (up-regulation). The trophic human chorionic gonadotropin (hCG) hormone did not impact AhR, its repressor AhRR or Cyp1b1 but it opposed the TCDD-enhanced AhRR mRNA levels. Conversely, TNFα stimulated AhR gene expression levels. Collectively, it is suggested that the impact of TCDD on expression of target genes in Leydig cells may operate under the complex network of hormones and cytokines.

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results