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1. Intestinal absorption of sphingosine: new insights on generated ceramide species using stable isotope tracing in vitro

Author: Catherine Calzada, David Cheillan, Nina Ritsch, Cécile Vors, Annie Durand, Sandra Pesenti, Magali Pettazzoni, Emmanuelle Meugnier, Marie-Caroline Michalski, and Armelle Penhoat
Subjects: chylomicrons, dietary fat, enterocytes, lipidomics, mass spectrometry, milk, Biochemistry, QD415-436
Abstract: Abstract: Dietary sphingomyelin (SM) has been reported to favorably modulate postprandial lipemia. Mechanisms underlying these beneficial effects on cardiovascular risk markers are not fully elucidated. Rodent studies showed that tritiated SM was hydrolyzed in the intestinal lumen into ceramides (Cer) and further to sphingosine (SPH) and fatty acids (FA) that were absorbed by the intestine. Our objective was to investigate the uptake and metabolism of SPH and/or tricosanoic acid (C23:0), the main FA of milk SM, as well as lipid secretion in Caco-2/TC7 cells cultured on semipermeable inserts. Mixed micelles (MM) consisting of different digested lipids and taurocholate were prepared without or with SPH, SPH and C23:0 (SPH+C23:0), or C23:0. Triglycerides (TG) were quantified in the basolateral medium, and sphingolipids were analyzed by tandem mass spectrometry. TG secretion increased 11-fold in all MM-incubated cells compared with lipid-free medium. Apical supply of SPH-enriched MM led to increased concentrations of total Cer in cells, and coaddition of C23:0 in SPH-enriched MM led to a preferential increase of C23:0 Cer and C23:0 SM. Complementary experiments using deuterated SPH demonstrated that SPH-d9 was partly converted to sphingosine-1-phosphate-d9, Cer-d9, and SM-d9 within cells incubated with SPH-enriched MM. A few Cer-d9 (2% of added SPH-d9) was recovered in the basolateral medium of (MM+SPH)-incubated cells, especially C23:0 Cer-d9 in (MM+SPH+C23:0)-enriched cells. In conclusion, present results indicate that MM enriched with (SPH+C23:0), such as found in postprandial micelles formed after milk SM ingestion, directly impacts sphingolipid endogenous metabolism in enterocytes, resulting in the secretion of TG-rich particles enriched with C23:0 Cer.
Published: 2024
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2. INFOGEST inter-laboratory recommendations for assaying gastric and pancreatic lipases activities prior to in vitro digestion studies

Author: Myriam M.L. Grundy, Evan Abrahamse, Annette Almgren, Marie Alminger, Ana Andres, Renata M.C. Ariëns, Shanna Bastiaan-Net, Claire Bourlieu-Lacanal, André Brodkorb, Maria R. Bronze, Irene Comi, Leslie Couëdelo, Didier Dupont, Annie Durand, Sedef N. El, Tara Grauwet, Christine Heerup, Ana Heredia, Marcos R. Infantes Garcia, Christian Jungnickel, Ilona E. Kłosowska-Chomiczewska, Marion Létisse, Adam Macierzanka, Alan R. Mackie, David J. McClements, Olivia Menard, Anne Meynier, Marie-Caroline Michalski, Ana-Isabel Mulet-Cabero, Anette Mullertz, Francina M. Payeras Perelló, Irene Peinado, Mélina Robert, Sébastien Secouard, Ana T. Serra, Sandra D. Silva, Gabriel Thomassen, Cecilia Tullberg, Ingrid Undeland, Carole Vaysse, Gerd E. Vegarud, Sarah H.E. Verkempinck, Michelle Viau, Mostafa Zahir, Ruojie Zhang, and Frédéric Carrière
Subjects: Lipases, Lipolysis, Enzyme activity, Titration method, Inhibitor, INFOGEST, Nutrition. Foods and food supply, TX341-641
Abstract: In vitro digestion studies often use animal digestive enzyme extracts as substitutes of human gastric and pancreatic secretions. Pancreatin from porcine origin is thus commonly used to provide relevant pancreatic enzymes such as proteases, amylase and lipase. Rabbit gastric extracts (RGE) have been recently introduced to provide gastric lipase in addition to pepsin. Before preparing simulated gastric and pancreatic extracts with targeted enzyme activities as described in in vitro digestion protocols, it is important to determine the activities of enzyme preparations using validated methods. The purpose of this inter-laboratory study within the INFOGEST network was to test the repeatability and reproducibility of lipase assays using the pH-stat technique for measuring the activities of gastric and pancreatic lipases from various sources. Twenty-one laboratories having different pH-stat devices received the same protocol with identical batches of RGE and two pancreatin sources. Lipase assays were performed using tributyrin as a substrate and three different amounts (50, 100 and 200 µg) of each enzyme preparation. The repeatability results within individual laboratories were satisfactory with coefficients of variation (CVs) ranging from 4 to 8% regardless of the enzyme amount tested. However, the inter-laboratory variability was high (CV > 15%) compared to existing standards for bioanalytical assays. We identified and weighted the contributions to inter-laboratory variability of several parameters associated with the various pH-stat equipment used in this study (e.g. reaction vessel volume and shape, stirring mode and rate, burette volume for the automated delivery of sodium hydroxide). Based on this, we established recommendations for improving the reproducibility of lipase assays using the pH-stat technique. Defining accurate and complete recommendations on how to correctly quantify activity levels of enzyme preparations is a gateway to promising comparison of in vitro data obtained from different laboratories following the same in vitro digestion protocol.
Published: 2021
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3. Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women

Author: Mélanie Le Barz, Cécile Vors, Emmanuel Combe, Laurie Joumard-Cubizolles, Manon Lecomte, Florent Joffre, Michèle Trauchessec, Sandra Pesenti, Emmanuelle Loizon, Anne-Esther Breyton, Emmanuelle Meugnier, Karène Bertrand, Jocelyne Drai, Chloé Robert, Annie Durand, Charlotte Cuerq, Patrice Gaborit, Nadine Leconte, Annick Bernalier-Donadille, Eddy Cotte, Martine Laville, Stéphanie Lambert-Porcheron, Lemlih Ouchchane, Hubert Vidal, Corinne Malpuech-Brugère, David Cheillan, and Marie-Caroline Michalski
Subjects: Clinical trials, Metabolism, Medicine
Abstract: BACKGROUND High circulating levels of ceramides (Cer) and sphingomyelins (SM) are associated with cardiometabolic diseases. The consumption of whole fat dairy products, naturally containing such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown.METHODS In a 4-week randomized controlled trial, 58 postmenopausal women daily consumed milk PL-enriched cream cheese (0, 3, or 5 g of milk PL). Postprandial metabolic explorations were performed before and after supplementation. Analyses included SM and Cer species in serum, chylomicrons, and feces. The ileal contents of 4 ileostomy patients were also explored after acute milk PL intake.RESULTS Milk PL decreased serum atherogenic C24:1 Cer, C16:1 SM, and C18:1 SM species (Pgroup < 0.05). Changes in serum C16+18 SM species were positively correlated with the reduction of cholesterol (r = 0.706), LDL-C (r = 0.666), and ApoB (r = 0.705) (P < 0.001). Milk PL decreased chylomicron content in total SM and C24:1 Cer (Pgroup < 0.001), parallel to a marked increase in total Cer in feces (Pgroup < 0.001). Milk PL modulated some specific SM and Cer species in both ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSION Milk PL supplementation decreased atherogenic SM and Cer species associated with the improvement of cardiovascular risk markers. Our findings bring insights on sphingolipid metabolism in the gut, especially Cer, as signaling molecules potentially participating in the beneficial effects of milk PL.TRIAL REGISTRATION ClinicalTrials.gov, NCT02099032, NCT02146339.FUNDING ANR-11-ALID-007-01; PHRCI-2014: VALOBAB, no. 14-007; CNIEL; GLN 2018-11-07; HCL (sponsor).
Published: 2021
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4. Addendum: Gouriou et al. ANT2-Mediated ATP Import into Mitochondria Protects against Hypoxia Lethal Injury. Cells 2020, 9, 2542

Author: Yves Gouriou, Muhammad Rizwan Alam, Zeina Harhous, Claire Crola Da Silva, Delphine Baetz, Sally Badawi, Etienne Lefai, Jennifer Rieusset, Annie Durand, Rania Harisseh, Abdallah Gharib, Michel Ovize, and Gabriel Bidaux
Subjects: n/a, Cytology, QH573-671
Abstract: The authors and the Cells Editorial Office would like to add the section “Materials and Methods”, which was missing in the original version [...]
Published: 2021
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5. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans.

Author: David Patsouris, Jingwei-Ji Cao, Guillaume Vial, Amelie Bravard, Etienne Lefai, Annie Durand, Christine Durand, Marie-Agnés Chauvin, Fabienne Laugerette, Cyrille Debard, Marie-Caroline Michalski, Martine Laville, Hubert Vidal, and Jennifer Rieusset
Subjects: Medicine, Science
Abstract: Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
Published: 2014
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6. A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women

Author: Marie Michèle Boulet, Catherine Calzada, Magali Pettazzoni, Taïssia Lelekov-Boissard, Charline Buisson, Mathilde Di Filippo, Annie Durand, Stéphanie Lambert-Porcheron, Julie-Anne Nazare, Philippe Moulin, Marie-Caroline Michalski, David Cheillan, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Hôpital Louis Pradel [CHU - HCL], Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), and CALZADA, Catherine
Subjects: GM3, triglyceride-rich lipoproteins ceramides, Sphingolipids, ceramides, [SDV]Life Sciences [q-bio], Lipoproteins, General Medicine, Palm Oil, Biochemistry, dietary lipids, sphingomyelins, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, tandem mass spectrometry, hazelnut-cocoa palm oil spread, Butter, Humans, chylomicrons, Female, type 2 diabetes, Triglycerides
Abstract: International audience; Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.
Published: 2022
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7. Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial

Author: Pauline Delage, Bérénice Ségrestin, Kévin Seyssel, Stéphanie Chanon, Aurélie Vieille-Marchiset, Annie Durand, Angéline Nemeth, Sylviane Métairon, Aline Charpagne, Patrick Descombes, Jörg Hager, Martine Laville, Hubert Vidal, and Emmanuelle Meugnier
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Molecular Biology, Biochemistry
Published: 2023
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8. Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles

Author: Audrey Jalabert, Audrey Villard-Garon, Sophie Rome, Annette Draeger, Pascal Colosetti, Christophe O. Soulage, Françoise Hullin-Matsuda, Isabelle Delton, Cyrille Bergerot, Céline Luquain-Costaz, Elisabeth Errazuriz-Cerda, Valentin Leuzy, Mathilde Di Filippo, Annie Durand, Baptiste Fourmaux, Maxence Rabia, René Köffel, Philippe Moulin, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie intégrative, cellulaire et moléculaire (PICM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM), and French Ministery of education Institut National de la Sante et de la Recherche Medicale (Inserm) University of Bern SFD (Societe Francophone du Diabete_AE 2016) VML (Vaincre les Maladies Lysosomales_convention AO2018-6)
Subjects: Male, 0301 basic medicine, THP-1 Cells, Endosome, [SDV]Life Sciences [q-bio], Phospholipid, Amiodarone, Pilot Projects, Endosomes, Exosomes, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Lysosomal storage diseases, medicine, Extracellular, Animals, Humans, 610 Medicine & health, Aged, Phospholipidosis, Kidney, 030102 biochemistry & molecular biology, CD63, Chemistry, Macrophages, Bis(monoacylglycero)phosphate, General Medicine, Middle Aged, Extracellular vesicles, Lysobisphosphatidic acid, Endolysosome, Microvesicles, Rats, Cell biology, Docosahexaenoic acid, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, interest, Monoglycerides, Female, Kidney Diseases, Lysophospholipids, Lysosomes, Anti-Arrhythmia Agents, Biomarkers
Abstract: International audience; Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes.
Published: 2020
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9. Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women

Author: Chloé Robert, Marie-Caroline Michalski, Nadine Leconte, Manon Lecomte, Laurie Joumard-Cubizolles, David Cheillan, Karène Bertrand, Anne-Esther Breyton, Emmanuel Combe, Annie Durand, Mélanie Le Barz, Florent Joffre, Martine Laville, Corinne Malpuech-Brugère, Cécile Vors, Michèle Trauchessec, Lemlih Ouchchane, Charlotte Cuerq, Sandra Pesenti, Patrice Gaborit, Hubert Vidal, Eddy Cotte, Jocelyne Drai, Stéphanie Lambert-Porcheron, Emmanuelle Meugnier, Emmanuelle Loizon, Annick Bernalier-Donadille, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Corps Gras, (ITERG), Hospices Civils de Lyon, Unité Maladies Héréditaires du Métabolisme, Service de Biochimie et Biologie, Centre, Hospices Civils de Lyon, Unité de Nutrition Endocrinologie Métabolisme, Service de Biochimie, ACTALIA, Dairy Products and Technologies, Science et Technologie du Lait et de l'Oeuf (STLO), AGROCAMPUS OUEST, 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microbiologie Environnement Digestif Santé (MEDIS), Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, Service de Chirurgie Digestive, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes (UGA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), 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), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, FUNDINGS. Agence Nationale de la Recherche, ANR-11-ALID-007-01, Regional Hospital Clinical Research Program (PHRCI-2014: VALOBAB, n°14-007), French Dairy Interbranch Organization (CNIEL), Groupe Lipides et Nutrition (GLN 2018-11-07), Hospices Civils de Lyon as sponsor., Giboulot, Anne, Actalia - division produits laitiers, Actalia [Saint-Lô], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, 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), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)
Subjects: 0301 basic medicine, chemistry.chemical_compound, Feces, 0302 clinical medicine, Cheese, maladie cardiovasculaire, Gastrointestinal tract, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, food and beverages, General Medicine, Cardiovascular disease, 3. Good health, Sphingomyelins, Postmenopause, Postprandial, Cholesterol, Milk, 030220 oncology & carcinogenesis, lipide polaire, Female, lipids (amino acids, peptides, and proteins), Sphingomyelin, medicine.medical_specialty, Ceramide, sphingomyéline, Ceramides, 03 medical and health sciences, intestin, Internal medicine, medicine, Animals, Humans, Clinical Trials, Lipid rafts, Glycoproteins, business.industry, lipide du lait, ménopause, Metabolism, Lipid Droplets, Overweight, Lipid Metabolism, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Endocrinology, chemistry, Clinical Medicine, Glycolipids, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Chylomicron
Abstract: International audience; BACKGROUND. High circulating levels of ceramides (Cer) and sphingomyelins (SM) have been associated with cardiometabolic diseases. The consumption of whole-fat dairy products, which naturally contain such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown. We investigated how milk PL supplementation impacts circulating and intestinal SM and Cer composition in association with improvement of cardiovascular markers.METHODS. In a 4 week-randomized double-blind controlled study, 58 postmenopausal women consumed daily a cream cheese containing 0, 3 or 5 g of milk PL. Postprandial metabolic explorations were performed before and after the supplementation. SM and Cer species were analyzed in serum, intestine-derived chylomicrons and feces. The ileal content of 4 ileostomy patients was also explored after milk PL intake in a crossover double-blind study.RESULTS. Milk PL consumption decreased serum atherogenic C24:1 Cer (Pgroup = 0.033), C16:1 (Pgroup = 0.007) and C18:1 (Pgroup = 0.003) SM species. Changes in serum C16+18 SM species were positively correlated with the reduction of total cholesterol (r = 0.706, P < 0.001), LDL-C (r = 0.666, P < 0.001) and ApoB (r = 0.705, P < 0.001). Milk PL decreased the concentration in chylomicrons of total SM (Pgroup < 0.0001) and of C24:1 Cer (Pgroup = 0.001). Saturated SM and Cer species, which are also the major species found in milk PL-enriched cheeses, increased in ileal efflux and feces. There was a marked increase in total fecal Cer after milk PL supplementation (Pgroup = 0.0002). Milk PL also modulated the abundance of some specific SM and Cer species in ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSION. These data demonstrate that milk PL supplementation decreases atherogenic SM and Cer species associated with an improvement of cardiovascular risk markers. Our findings bring new insights on sphingolipid metabolism in the gastrointestinal tract, especially Cer as such signaling molecules potentially participating in the beneficial effect of milk PL. ClinicalTrials.gov, NCT02099032, NCT02146339.
Published: 2021
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10. Homogeneous triacylglycerol tracers can impact fat crystallization and its lipolysis rate under simulated physiological conditions

Author: Frédéric Carrière, Cécile Vors, Marie-Caroline Michalski, Carole Knibbe, Sabine Danthine, Annie Durand, Marion Létisse, Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Bioénergétique et Ingénierie des Protéines (BIP ), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2), 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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Homogeneous, law, Chemistry, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV]Life Sciences [q-bio], Biophysics, [CHIM.CRIS]Chemical Sciences/Cristallography, Lipolysis, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Crystallization, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS, law.invention
Abstract: International audience
Published: 2020

11. Addendum: Gouriou et al. ANT2-Mediated ATP Import into Mitochondria Protects against Hypoxia Lethal Injury. Cells 2020, 9, 2542

Author: Rania Harisseh, Michel Ovize, Sally Badawi, Zeina Harhous, Muhammad Rizwan Alam, Abdallah Gharib, Annie Durand, Delphine Baetz, Gabriel Bidaux, Etienne Lefai, Yves Gouriou, Jennifer Rieusset, and Claire Crola Da Silva
Subjects: n/a, QH301-705.5, Chemistry, medicine, Addendum, General Medicine, Biology (General), Mitochondrion, Hypoxia (medical), medicine.symptom, Cell biology
Abstract: The authors and the Cells Editorial Office would like to add the section “Materials and Methods”, which was missing in the original version [...]
Published: 2021
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12. Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets

Author: Manon Lecomte, Emmanuelle Loizon, Carole Vaysse, Pascale Plaisancié, Alain Géloën, Annie Durand, Marie-Caroline Michalski, Leslie Couëdelo, Florent Joffre, Emmanuelle Meugnier, 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), Institut des Corps Gras (ITERG), ITERG, Université Panthéon-Sorbonne - UFR d'Économie (UP1 UFR02), Université Panthéon-Sorbonne (UP1), ITERG (ITERG), 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 Multidisciplinaire de Biochimie des Lipides (IMBL), Covalab-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Oméga 21, and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Male, 0301 basic medicine, endotoxin, Panniculitis, huile de palme, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Lipopolysaccharide Receptors, tissu adipeux, Adipose tissue, White adipose tissue, endotoxine, Biochemistry, Lecithin, chemistry.chemical_compound, 0302 clinical medicine, Food science, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, palm oil, Membrane Glycoproteins, Nutrition and Dietetics, alpha-Linolenic acid, Fatty Acids, adipose tissue, Liver, lipide polaire, medicine.symptom, Lipopolysaccharide binding protein, food.ingredient, Dietary lipid, 030209 endocrinology & metabolism, Inflammation, Biology, Diet, High-Fat, 03 medical and health sciences, food, medicine, Animals, soja, Molecular Biology, soya bean, huile de lin, Fatty acid, linseed oil, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Dietary Supplements, biology.protein, Soybeans, Carrier Proteins, Acute-Phase Proteins
Abstract: Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoiins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as alpha-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.
Published: 2017
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13. Le profil en sphingolipides circulants est modifié par un apport en sphingolipides alimentaires via une supplémentation en lipides polaires laitiers chez des femmes ménopausées à risque cardiovasculaire

Author: Mélanie Le Barz, Cécile Vors, Laurie Joumard-Cubizolles, Emmanuel Combe, Joffre, F., Ouchchane, L., Chloe Robert, Annie Durand, Raynal, K., Nadine Leconte, Hubert Vidal, Laville, M., Lambert-Porcheron, S., Corinne Malpuech-Brugère, David Cheillan, Marie-Caroline Michalski, 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), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut des corps gras (ITERG), Centre National de la Recherche Scientifique (CNRS), Actalia [Saint-Lô], Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), 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]), Hospices Civils de Lyon (HCL), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Institut National de Recherche Agronomique (INRA). UMR UMR INRA / AgroCampus Rennes : Science et Technologie du Lait et de l'?uf (1253)., Actalia, 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), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble
Subjects: sphingolipide, risque cardiovasculaire, [SDV.IDA]Life Sciences [q-bio]/Food engineering, lipide polaire, ménopause, supplémentation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS, produit laitier
Abstract: International audience
Published: 2019

14. Milk Polar Lipids in a High-Fat Diet Can Prevent Body Weight Gain: Modulated Abundance of Gut Bacteria in Relation with Fecal Loss of Specific Fatty Acids

Author: David Cheillan, Marie-Caroline Michalski, Karène Bertrand, Charline Buisson, Marine Milard, Pascale Plaisancié, Laure B. Bindels, Florent Joffre, Sébastien Viel, Valérie Sauvinet, Nathalie M. Delzenne, Audrey M. Neyrinck, Emmanuelle Loizon, Lydie Humbert, Annie Durand, Corinne Louche-Pelissier, Emmanuelle Meugnier, Dominique Rainteau, Fabienne Laugerette, Lorna Garnier, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Louvain Drug Research Institute, 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), 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]), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Corps Gras (ITERG), ITERG, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition and Metabolism Research Group (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL), French Ministry for Higher Education and Research via EDISS, Universite Claude Bernard Lyon 1, CNIEL (French Dairy Interbranch Organization), 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), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), 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), 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 de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Michalski, Marie-Caroline
Subjects: Male, 0301 basic medicine, obesity, sphingomyeline, [SDV]Life Sciences [q-bio], Ingénierie des aliments, Gut flora, Weight Gain, [SDV.IDA]Life Sciences [q-bio]/Food engineering, adiposity, bile salts, feces, gut barrier, microbiota, milk fat globule membrane, phospholipids, sphingomyelin, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, biology, acide gras, Chemistry, Fatty Acids, sel biliaire, Lipids, Sphingomyelins, Bifidobacterium animalis, obésité, Milk, Liver, medicine.symptom, Sphingomyelin, Biotechnology, phospholipide, medicine.medical_specialty, Crypt, Inflammation, Diet, High-Fat, 03 medical and health sciences, microbiote, lipid, Internal medicine, medicine, Food engineering, Animals, Feces, lipide, 030109 nutrition & dietetics, Macrophages, barrière intestinale, biology.organism_classification, medicine.disease, Obesity, Gastrointestinal Microbiome, Lactobacillus reuteri, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Intestinal Absorption, fatty acid, Food Science
Abstract: Scope Enhanced adiposity and metabolic inflammation are major features of obesity associated with altered gut microbiota and intestinal barrier. How these metabolic outcomes can be impacted by milk polar lipids (MPL), naturally containing 25% of sphingomyelin, is investigated in mice fed a mixed high-fat (HF) diet . Methods and results Male C57Bl/6 mice receive a HF-diet devoid of MPL (21% fat, mainly palm oil, in chow), or supplemented with 1.1% or 1.6% of MPL (HF-MPL1; HF-MPL2) via a total-lipid extract from butterserum concentrate for 8 weeks. HF-MPL2 mice gain less weight versus HF (p < 0.01). Diets do not impact plasma markers of inflammation but in the liver, HF-MPL2 tends to decrease hepatic gene expression of macrophage marker F4/80 versus HF-MPL1 (p = 0.06). Colonic crypt depth is the maximum in HF-MPL2 (p < 0.05). In cecal microbiota, HF-MPL1 increases Bifidobacterium animalis versus HF (p < 0.05). HF-MPL2 decreases Lactobacillus reuteri (p < 0.05), which correlates negatively with the fecal loss of milk sphingomyelin-specific fatty acids (p < 0.05). Conclusion In mice fed a mixed HF diet, MPL can limit HF-induced body weight gain and modulate gut physiology and the abundance in microbiota of bacteria of metabolic interest. This supports further exploration of how residual unabsorbed lipids reaching the colon can impact HF-induced metabolic disorders.
Published: 2019
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15. Homogeneous triacylglycerol tracers have an impact on the thermal and structural properties of dietary fat and its lipolysis rate under simulated physiological conditions

Author: Damien Agopian, Marie-Caroline Michalski, Annie Durand, Frédéric Carrière, Marion Létisse, Sabine Danthine, Romain Guyon, Cécile Vors, Carole Knibbe, Gembloux Agro-Bio Tech [Gembloux], Université de Liège, 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), Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre National Interprofessionnel de l'Economie Laitiere (CNIEL, French Dairy Interbranch Organization) INRA CNIEL, 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 National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), and Carrière, Frédéric
Subjects: Lipolysis, [SDV]Life Sciences [q-bio], 030303 biophysics, Melting profile, Biochemistry, Intestinal absorption, 03 medical and health sciences, chemistry.chemical_compound, Differential scanning calorimetry, TRACER, Food science, Triolein, Polymorphism, Molecular Biology, Triglycerides, 030304 developmental biology, 0303 health sciences, Molecular Structure, Chemistry, Organic Chemistry, fungi, Temperature, Cell Biology, Lipid, Dietary Fats, X-ray diffraction, [SDV] Life Sciences [q-bio], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Tripalmitin, Anhydrous, Digestion, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Dietary fats are present in the diet under different types of structures, such as spread vs emulsions (notably in processed foods and enteral formula), and interest is growing regarding their digestion and intestinal absorption. In clinical trials, there is often a need to add stable isotope-labeled triacylglycerols (TAGs) as tracers to the ingested fat in order to track its intestinal absorption and further metabolic fate. Because most TAG tracers contain saturated fatty acids, they may modify the physicochemical properties of the ingested labeled fat and thereby its digestion. However, the actual impact of tracer addition on fat crystalline properties and lipolysis by digestive lipases still deserves to be explored. In this context, we monitored the thermal and polymorphic behavior of anhydrous milk fat (AMF) enriched in homogeneous TAGs tracers and further compared it with the native AMF using differential scanning calorimetry and power X-ray diffraction. As tracers, we used a mixture of tripalmitin, triolein and tricaprylin at 2 different concentrations (1.5 and 5.7 wt%, which have been used in clinical trials). The addition of TAG tracers modified the AMF melting profile, especially at the highest tested concentration (5.7 wt%). Both AMF and AMF enriched with 1.5 wt% tracers were completely melted around 37 °C, i.e. close to the body temperature, while the AMF enriched with 5.7 wt% tracers remained partially crystallized at this temperature. Similar trends were observed in both bulk and emulsified systems. Moreover, the kinetics of AMF polymorphic transformation was modified in the presence of tracers. While only β’ form was observed in the native AMF, the β-form was clearly detected in the AMF containing 5.7 wt% tracers. We further tested the impact of tracers on the lipolysis of AMF in bulk using a static in vitro model of duodenal digestion. Lipolysis of AMF enriched with 5.7 wt% tracers was delayed compared with that of AMF and AMF enriched with 1.5 wt% tracers. Therefore, low amounts of TAG tracers including tripalmitin do not have a high impact on fat digestion, but one has to be cautious when using higher amounts of these tracers.
Published: 2019
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16. Acute effects of milk polar lipids on intestinal tight junction expression: Towards an impact of sphingomyelin through the regulation of IL-8 secretion?

Author: David Cheillan, Karène Bertrand, Emmanuelle Loizon, Lorna Garnier, Fabienne Laugerette, Florent Joffre, Charline Buisson, Marie-Caroline Michalski, Sébastien Viel, Armelle Penhoat, Marine Milard, Annie Durand, Emmanuelle Meugnier, 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), ITERG, Service de Biochimie et Biologie Moléculaire Grand Est, Centre de Biologie et de Pathologie Est[Lyon], Hospices Civils de Lyon (HCL), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], French Ministry for Higher Education and Research via EDISS, Universite Claude Bernard Lyon 1, CNIEL (French Dairy Interbranch Organization), 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 International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, 0301 basic medicine, Chemokine CXCL1, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Chemokine CXCL2, Clinical Biochemistry, Occludin, Biochemistry, Tight Junctions, Proinflammatory cytokine, 03 medical and health sciences, Gene expression, cytokine, Animals, Humans, Secretion, Molecular Biology, reproductive and urinary physiology, phospholipid, Tight Junction Proteins, 030109 nutrition & dietetics, Nutrition and Dietetics, Dose-Response Relationship, Drug, Tight junction, gut barrier, Chemistry, Interleukin-8, virus diseases, Lipid metabolism, Lipids, Molecular biology, Sphingomyelins, Intestines, Mice, Inbred C57BL, Milk, 030104 developmental biology, Gene Expression Regulation, Caco-2, caco-2, dairy, Caco-2 Cells, Sphingomyelin, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, milk fat globule membrane
Abstract: International audience; Milk polar lipids (MPL) are specifically rich in milk sphingomyelin (MSM) which represents 24% of MPL. Beneficial effects of MPL or MSM have been reported on lipid metabolism, but information on gut physiology is scarce. Here we assessed whether MPL and MSM can impact tight junction expression. Human epithelial intestinal Caco-2/TC7 cells were incubated with mixed lipid micelles devoid of MSM (Control) or with 0.2 or 0.4 mM of MSM via pure MSM or via total MPL. C57Bl/6 mice received 5 or 10 mg of MSM via MSM or via MPL (oral gavage); small intestinal segments were collected after 4 h. Impacts on tight junction and cytokine expressions were assessed by qPCR; IL-8 and IL-8 murine homologs (Cxcl1, Cxcl2) were analyzed. In vitro, MSM increased tight junction expression (Occludin, ZO-1) vs Control, unlike MPL. However, no differences were observed in permeability assays (FITC-dextran, Lucifer yellow). MSM increased the secretion and gene expression of IL-8 but not of other inflammatory cytokines. Moreover, cell incubation with IL-8 induced an overexpression of tight junction proteins. In mice, mRNA level of Cxcl1 and Cxcl2 in the ileum were increased after gavage with MSM vs NaCl but not with MPL. Altogether, these results suggest a specific action of MSM on intestinal tight junction expression, possibly mediated by IL-8. Our study provides clues to shed light on the beneficial effects of MPL on intestinal functions and supports the need for further mechanistic exploration of the direct vs indirect effects of MSM and IL-8 on the gut barrier.
Published: 2019
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17. Human milk pasteurisation reduces pre-lipolysis but not digestive lipolysis and moderately decreases intestinal lipid uptake in a combination of preterm infant in vitro models

Author: Armelle Penhoat, Rachel Buffin, Annie Durand, Olivia Ménard, Carole Knibbe, Jean-Charles Picaud, Marine Vincent, Jordane Ossemond, Emmanuelle Loizon, Marie-Caroline Michalski, Didier Dupont, Julie Etienne, Amélie Deglaire, Emmanuelle Meugnier, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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 National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Néonatalogie [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, 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), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), SFMP (French Society of Perinatal Medicine)., Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-AGROCAMPUS OUEST, 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-Université Lumière - Lyon 2 (UL2)-Inria Grenoble - Rhône-Alpes, and Giboulot, Anne
Subjects: Lipolysis, [SDV]Life Sciences [q-bio], Pasteurization, Absorption (skin), In vitro static digestion, 01 natural sciences, Intestinal absorption, Cell Line, Analytical Chemistry, law.invention, chemistry.chemical_compound, 0404 agricultural biotechnology, law, Lipid droplet, Humans, Food science, Intestinal Mucosa, Caco-2 cells, chemistry.chemical_classification, Milk, Human, Triglyceride, Human milk, 010401 analytical chemistry, Infant, Newborn, Lipid absorption, Fatty acid, 04 agricultural and veterinary sciences, General Medicine, Lipids, 040401 food science, 0104 chemical sciences, Intestines, [SDV] Life Sciences [q-bio], Pasteurisation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, Digestion, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Lipid digestion, Infant, Premature, Food Science
Abstract: International audience; Donor human milk, pasteurised for safety reasons, is the first alternative for feeding preterm infants when mothers' own milk is unavailable. Breastmilk pasteurisation impact on lipid digestion and absorption was evaluated by a static in vitro digestion model for preterm infants coupled with intestinal absorption using Caco-2/TC7 cells. Lipid absorption was quantified by digital image analysis of lipid droplets, by measurement of basolateral triglyceride concentration and by analysing the expression of major genes involved. After in vitro digestion, lipolysis extent was 13% lower in pasteurised human milk (PHM) than in raw human milk (RHM). In Caco-2/TC7 cells, the number of lipid droplets was identical for both milk types, while the mean droplet area was 17% smaller with PHM. Altogether, pasteurisation decreased the pre-lipolysis of human milk. This initial difference in free fatty acid amount was only partially buffered by the subsequent processes of in vitro digestion and cellular lipid absorption.
Published: 2020
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18. Metabolic effects in mice of cream formulation: Addition of both thickener and emulsifier does not alter lipid metabolism but modulates mucus cells and intestinal endoplasmic reticulum stress

Author: Charline Buisson, Pascale Plaisancié, S. Bugeat, Marion Létisse, Emmanuelle Loizon, Alain Géloën, S. Serieye, Emmanuelle Meugnier, Marie-Caroline Michalski, Annie Durand, Fabienne Laugerette, Marine Milard, 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), Laboratoire de Spectrochimie Infrarouge et Raman - UMR 8516 (LASIR), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Laboratoire d'ingénierie circulation transports (LICIT), Institut National de Recherche sur les Transports et leur Sécurité (INRETS)-École Nationale des Travaux Publics de l'État (ENTPE), 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), Sodiaal Union, Partenariat industriel : SODIAAL-CANDIA R&D; Sodiaal-Candia RD, Sodiaal-Candia RI, CNIEL (French Dairy Interbranch Organization, Paris, France), Nutricia Research (Utrecht, the Netherlands), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), 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), and ProdInra, Migration
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Duodenum, [SDV]Life Sciences [q-bio], cow milk, Fatty Acids, Nonesterified, dairy matrix, Mice, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, Intestine, Small, Genetics, medicine, Animals, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Intestinal permeability, Chemistry, Endoplasmic reticulum, Intestinal lipid absorption, Lipid metabolism, Endoplasmic Reticulum Stress, Lipid Metabolism, medicine.disease, Mucus, Small intestine, 3. Good health, Carrageenan, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Milk, nutrition, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Liver, Emulsifying Agents, carrageenan, Cattle, Food Additives, Animal Science and Zoology, Dairy Products, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Additives stabilize or improve the organoleptic or functional properties (or both) of many dairy products including whipping cream. Their influence on the metabolic effect of dairy cream is scarcely known. We tested the hypothesis that added emulsifier (lactic acid esters of mono- and diglycerides; MAG/DAG), thickener (carrageenan, CGN), or both, could modify the metabolic effect, notably in the intestine and liver. Nine-week-old male C57Bl/6J mice were fed UHT cream (indirect treatment) mixed with nonlipidic powder (final: 13% milkfat) for 1 or 4 wk. We compared creams (1) without additive (Ctl), (2) with thickener (Th), 0.02% of κ-CGN, and (3) with both thickener and emulsifier, 0.1% of MAG/DAG esters (Th/Em). We analyzed plasma parameters, intestine, and liver. Fasting glycemia, insulinemia, triglyceridemia, nonesterified fatty acids, body weight gain, and liver weight did not differ among groups. After 1 wk, Th/Em had higher expression in the duodenum of some of the genes involved in (1) intestinal lipid absorption and (2) tight junction proteins versus Ctl and Th. After 4 wk, mucus cell number in the small intestine was higher in Th/Em versus Ctl and Th. Genes involved in endoplasmic reticulum (ER) stress in the duodenum were more expressed in Th/Em after 1 wk. After 4 wk, in the colon, a higher expression of ER stress genes was observed for Th versus Th/Em and Ctl. Liver damage score was not altered by additives. Adding both CGN (0.02%) and MAG/DAG esters (0.1%) in dairy cream did not result in deleterious outcomes in mice after 4 wk regarding lipid metabolism, intestinal permeability, and liver disorders. The longer term effect of intestinal ER stress modulation deserves further investigation.
Published: 2018
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19. Metabolic effects in mice of cream processing: Direct ultra-high-temperature process lowers high-fat-induced adipose tissue inflammation

Author: Marie-Caroline Michalski, Alain Géloën, Emmanuelle Meugnier, Charline Buisson, Pascale Plaisancié, Marion Létisse, Emmanuelle Loizon, S. Serieye, S. Bugeat, Fabienne Laugerette, Annie Durand, Marine Milard, 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Sodiaal Union, Partenariat industriel : SODIAAL-CANDIA R&D; Sodiaal-Candia R&I (Research & Innovation Department, Paris, France), Sodiaal-Candia RI, CNIEL (French Dairy Interbranch Organization, Paris, France), and Nutricia Research (Utrecht, the Netherlands)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Hot Temperature, cow milk, Adipose tissue, Inflammation, dairy matrix, Fatty acid-binding protein, Fats, Butterfat, Mice, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Genetics, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Epididymis, 2. Zero hunger, 030109 nutrition & dietetics, Chemistry, Lipid metabolism, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Carrageenan, Intestines, Mice, Inbred C57BL, Milk, nutrition, Endocrinology, Adipose Tissue, Zonula Occludens-1 Protein, Microsome, Cattle, Animal Science and Zoology, Dairy Products, medicine.symptom, food process, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Although UHT heat treatment is being optimized to improve the stability and functional properties of dairy products, its metabolic effects remain scarcely known. As such, we studied the effect of the type of UHT process on lipid metabolism, intestinal barrier, and inflammation in mice. Nine-week-old male C57Bl/6J mice were fed a diet composed of nonlipidic powder mixed with different UHT dairy creams (final: 13% milkfat) for 1 or 4 wk. All creams contained 0.02% of thickener (carrageenan) and were treated via either (1) classical indirect heating process (Th), (2) indirect process at higher temperature (Th+), or (3) direct process by steam injection (ThD). Plasma, epididymal adipose tissue (EAT), and intestine were analyzed. Multivariate principal component analyses were used to identify differential effects of processes. Th+ differed by a globally higher liver damage score compared with that of the other creams. After 4 wk, the duodenal expression of lipid absorption genes fatty acid binding protein 4 (Fatp4) and microsomal triglycerides transfer protein (Mttp) was lower in the Th+ versus Th group. Expression in the colon of tight junction protein zonula occludens 1 (Zo-1) and of some endoplasmic reticulum stress markers was lower in both Th+ and ThD versus the Th group. In EAT, ThD had lower gene expression of several inflammatory markers after 4 wk. Some differential effects may be related to heat-induced physicochemical changes of creams. The type of cream UHT process differentially affected metabolic parameters in mice after a 4-wk fat-rich diet, partly due to cream structure. Altogether, direct steam injection process induced the lowest early markers of high-fat-induced metabolic inflammation in EAT.
Published: 2018
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20. Modulation de l’expression des protéines de jonctions serrées par la sphingomyéline, un lipide polaire naturellement présent dans les produits laitiers, via l’interleurkine-8

Author: M. Milard, Emmanuelle Loizon, Annie Durand, Fabienne Laugerette, Emmanuelle Meugnier, and Marie-Caroline Michalski
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Introduction et but de l’etude Les regimes occidentaux sont impliques dans le developpement des maladies metaboliques, dont la composante inflammatoire peut etre due a une alteration de la barriere intestinale. Les produits laitiers contiennent naturellement la matiere grasse sous forme de globule gras, constitues (i) d’un cœur de triglycerides (98 % des lipides) et (ii) d’une membrane biologique riche en lipides mineurs bioactifs, les lipides polaires (2 % des lipides) incluant de maniere specifique la sphingomyeline (SM, ∼ 25 % des lipides polaires). Les composes alimentaires peuvent affecter la barriere intestinale en influencant l’organisation des proteines des jonctions serrees qui sont impliquees dans les transports paracellulaires entre la lumiere intestinale et la circulation. Notre hypothese est que la matiere grasse laitiere exerce certains de ses effets benefiques par l’intermediaire de la SM, notamment sur l’integrite de la barriere intestinale qui pourraient reduire une inflammation. Nous avons teste in vitro l’hypothese que l’interleurkine-8 (IL-8), impliquee dans la maturation de l’epithelium intestinal [1] , serait un acteur des modifications intestinales en reponse aux lipides polaires laitiers. Materiel et methodes Des cellules Caco-2/TC7 cultivees sur filtre Transwell® (modele d’epithelium intestinal) ont ete incubees avec des micelles mixtes lipidiques enrichies ou non en SM laitiere (0 mM, 0,2 mM et 0,4 mM). L’expression genique des proteines impliquees dans les jonctions serrees (Occludine, claudine et JAM-1, des proteines transmembranaires, et ZO-1, proteine intracellulaire) et la concentration d’IL-8 (au pole apical et basolateral) ont ete etudies ainsi que plusieurs marqueurs inflammatoires. Nous avons dans un deuxieme temps incube les cellules avec l’IL-8 recombinante humaine en apical et/ou en basolateral afin d’observer l’impact sur l’expression genique des proteines de jonctions serrees. Resultats et analyse statistique Apres 24 h d’incubation avec des micelles enrichies avec 0,4 mM de SM, nous avons observe une surexpression de l’occludine (p Conclusion Nos resultats revelent un impact de la SM laitiere sur la modulation de l’expression des proteines des jonctions serrees et de l’IL-8, ainsi que de sa concentration. Apres incubation avec l’IL-8 recombinante, nous avons demontre que les modifications induites par la SM sur les jonctions serrees peuvent etre expliquees au moins en partie par l’action de l’IL-8.
Published: 2018
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21. Impact des lipides polaires laitiers sur le gain de poids, le microbiote et des marqueurs de la barrière intestinale in vivo et rôle de la sphingomyéline in vitro

Author: M. Milard, C. Buisson, Emmanuelle Meugnier, Nathalie M. Delzenne, Audrey M. Neyrinck, Marie-Caroline Michalski, V. Sauvinet, Emmanuelle Loizon, A. Penhoat, Laure B. Bindels, Annie Durand, and Fabienne Laugerette
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine
Published: 2019
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22. Front cover: Milk Polar Lipids in a High-Fat Diet Can Prevent Body Weight Gain: Modulated Abundance of Gut Bacteria in Relation with Fecal Loss of Specific Fatty Acids

Author: Marine Milard, Fabienne Laugerette, Annie Durand, Charline Buisson, Emmanuelle Meugnier, Emmanuelle Loizon, Corinne Louche-Pelissier, Valérie Sauvinet, Lorna Garnier, Sébastien Viel, Karène Bertrand, Florent Joffre, David Cheillan, Lydie Humbert, Dominique Rainteau, Pascale Plaisancié, Laure B. Bindels, Audrey M. Neyrinck, Nathalie M. Delzenne, and Marie-Caroline Michalski
Subjects: Food Science, Biotechnology
Published: 2019
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23. Depressing Mitochondria-Reticulum Interactions Protects Cardiomyocytes From Lethal Hypoxia-Reoxygenation Injury

Author: Alain Lacampagne, Emily Tubbs, Jennifer Rieusset, Claire Crola Da Silva, Geoffrey Teixeira, Jérémy Fauconnier, Michel Ovize, Melanie Paillard, Ludovic Gomez, Elise Belaidi, Annie Durand, Pierre-Alain Thiebaut, Maryline Abrial, Nathan Mewton, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Université Montpellier 2 - Sciences et Techniques (UM2), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Louis Pradel [CHU - HCL], CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-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), 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), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Paillard, Mélanie
Subjects: Male, Patch-Clamp Techniques, [SDV]Life Sciences [q-bio], Myocardial Reperfusion Injury, In Vitro Techniques, Biology, Mitochondrion, Endoplasmic Reticulum, Mitochondria, Heart, Cell Line, Cyclophilins, Mice, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Animals, Inositol 1,4,5-Trisphosphate Receptors, HSP70 Heat-Shock Proteins, Myocytes, Cardiac, Calcium Signaling, Patch clamp, Cells, Cultured, 030304 developmental biology, Calcium signaling, Mice, Knockout, 0303 health sciences, Voltage-Dependent Anion Channel 1, Endoplasmic reticulum, Membrane Proteins, Intracellular Membranes, medicine.disease, Cell Hypoxia, Rats, Cell biology, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Oxygen, Mitochondrial matrix, Multiprotein Complexes, 030220 oncology & carcinogenesis, Chaperone (protein), biology.protein, Cardiology and Cardiovascular Medicine, VDAC1, Reperfusion injury, Cyclophilin D
Abstract: Background— Under physiological conditions, Ca 2+ transfer from the endoplasmic reticulum (ER) to mitochondria might occur at least in part at contact points between the 2 organelles and involves the VDAC1/Grp75/IP3R1 complex. Accumulation of Ca 2+ into the mitochondrial matrix may activate the mitochondrial chaperone cyclophilin D (CypD) and trigger permeability transition pore opening, whose role in ischemia/reperfusion injury is well recognized. We questioned here whether the transfer of Ca 2+ from ER to mitochondria might play a role in cardiomyocyte death after hypoxia-reoxygenation. Methods and Results— We report that CypD interacts with the VDAC1/Grp75/IP3R1 complex in cardiomyocytes. Genetic or pharmacological inhibition of CypD in both H9c2 cardiomyoblasts and adult cardiomyocytes decreased the Ca 2+ transfer from ER to mitochondria through IP3R under normoxic conditions. During hypoxia-reoxygenation, the interaction between CypD and the IP3R1 Ca 2+ channeling complex increased concomitantly with mitochondrial Ca 2+ content. Inhibition of either CypD, IP3R1, or Grp75 decreased protein interaction within the complex, attenuated mitochondrial Ca 2+ overload, and protected cells from hypoxia-reoxygenation. Genetic or pharmacological inhibition of CypD provided a similar effect in adult mice cardiomyocytes. Disruption of ER-mitochondria interaction via the downregulation of Mfn2 similarly reduced the interaction between CypD and the IP3R1 complex and protected against hypoxia-reoxygenation injury. Conclusions— Our data (1) point to a new role of CypD at the ER-mitochondria interface and (2) suggest that decreasing ER-mitochondria interaction at reperfusion can protect cardiomyocytes against lethal reperfusion injury through the reduction of mitochondrial Ca 2+ overload via the CypD/VDAC1/Grp75/IP3R1 complex.
Published: 2013
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24. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Author: Odile Fremin-Batteux, Juliette Clarissou-Philippe, Benoît Jauhlac, Severine Guyetand, Jacques Gasnault, Corinne Haioun, Liamine Aissaoui, Marie-Christine Pages, Marie-Pierre Fos, Christian Rose, Didier Hubert, Marie-Rose Rothe, N. Bouziges, Benoît Huc, François Devianne, Sabine Bidart, Anne Forest, Kevin Bertrand, Mohamed Eldeghedy, Annick Verhaeghe, Caroline Malderet, Anne Bertrou, Bernard Guerquin, Catherine Duche, Muriel Archambaud, Rabea Cotteret, Olivier Toullalan, Yves Devaux, Smail Bergheul, Valérie Sivadon-Tardy, Pierre-Gilles Merville, Geneviève Blanchard-Marche, Didier Raoult, Bernard Hory, Florence Richardin, Evelyne Belle, Mohamed Menouar, K Guitteaud, Mohamad Mohty, Ambroise Montcriol, Max Laurin, Aurélia Picard, Jean-Paul Mira, Marie-Charlotte Chopin, Richard Bonnet, Michel Wolff, Sébastien Maillez, Jeanne Maugein, Véronique Leblond, Nicola Walid, Bernard Gauche, Mathieu Evillard, Hassen Jeddi, Anne Bourlet, Isabelle Grawey, Thierry Jault, Sandrine Hiret, Valerie Gaborieau, Véronique Boin-Gay, An Kim, Thierry Constans, Jean-François Gaide, Martine Giraud, Eric Meaudre Desgouttes, Alain Fur, Abdallah Maakaroun, Olivier Matray, Bertrand Maubert, Frédérique Péchinot, Aurelie Garbi, Claire Delbrouck, Benoît Grandclerc, Vincent Cadiergue, Hervé Lécuyer, Bernadette Grignon, Thierry Bensaid, Nicole Constantin, Yannick Chevalier, Hassène Rahmani, Thierry Levent, Joelle Desliers, Florence Van de Velde, Xavier Adhoute, Clara Andriau, Christophe Charasse, Rémi Vatan, Benoît Martha, Alain Lecis, Didier Albert, Romain Jacobs, Hélène Lefranc, Christian Martin, Nasseur Rezgui, Bertrand Pigeon, Catherine Le Henaff, Dominique Cassignard, Françoise Cotes, Eric Pujade Lauraine, Jean-François Gattault, Nicole Ferreira-Maident, Noémie Jourde-Chiche, Hélène Garrec, Olivier Darchen, Carole Schwebel, Marie-Christine Bezian, Patrick Daoud, Tsouria Becaid, Simone Laluque, David Broche, Christine Boisselier, Pascale Martres, Sarah Hammami, Brigitte Olivier, Jean-Marie Nkunzimana, Eric Monlun, Isabelle Marterl-Lafay, Marion Carboni, Marie-Françoise Mattei, Sandrine Castelin, Isabelle Barillot, Marie-Noelle Cufi, Thomas Kaiser, Catherine Herry, Pascal Hutin, Jean-Pierre Bronowicki, Bernard Branger, Pierre Thomas, Elie Zagdoun, Anne Goquelin, Ziad Assaf, Ingrid Croquet, Bruno Pozzetto, Thomas Similowski, Anne-Isabelle Briere, Marie-Thérèse Albertini, Mariam Blaka, Christelle Tassot, Anne Gaschet, Jean-Philippe Lavigne, Antoine Pujol, Philippe Colombat, Edouard Devaud, Hana Talabani-Boizot, François Barière, Anne-Marie Cordier, Philippe Gueudet, Georges Simon, Anne-Sophie Lipovac, Françoise Bandaly, Anne Beauplet-Lepage, Sylvie Prince, Charlotte Jouzel, Jean-Luc Deboutin, Patrick Zavadil, Louis Puybasset, Marie-Cécile Petit, Loïc Guillevin, Kamel Touati, Christophe Ntalu Nkato, Sylvie Carette, Jacques Vaucel, Chantal Delasalle, Marine Gross Goupil, Laurent Gutmann, Christiane Payen, Annick Barboteau, Firouzé Bani-Sadr, Christophe Legendre, Philippe Roulier, Elie Azria, Ibrahim Farah, Isabelle Rouquette-Vincent, Anne-Sophie Erena-Penet, Philippe Labadie, Eric Josien, Aicha Derragui, Mathieu Legrand, Odile Beyne-Rauzy, Jean-Marc Nabholtz, Marie-Joelle Demarcq, Olivier Garosi, Michel Deiber, Fabrice Chaix, Bertrand Souweine, Anne Collignon, Gisèle Renard, Mickael Jego, Gilles Bernardin, Anne Allart, Jocelyn Barrier, Marc Vasse, Philippe Ménager, Marc Wurmser, Abderkader Ouazir, Olivier Gontieron, Yvon Berland, Sébastien Trouiller, David Leysenne, Christophe Ozanon, Fanny Autret, Tahar Saghi, Loïc Dopeux, Sophie Benoit-Coustou, T. Fraisse, Christine Maillard, Karine Nikodijevic, Georges Kaltenbach, Angéline Jamet, Philippe Aucher, Julie Bottero, Marie-Claude Piffaut, Marianne Besnard, Florence Courillon, Marie Bonfils, Christine Ghevaert, Marie Destors, Eliette Jeanmaire, Franck Zerbib, Manuel-Luis Gameiro, T Prazuck, Laurent Mandin, Olivier Guisset, Marguerite Fines, Toufik Feddal, Agnès Jouffret, Louis Mesnard, Thomas Bourrée, Hasinrina Razafimahefa, Sylvestre Tigaud, Vincent Estève, Philippe Malherbe, Jean-Michel Salord, Pascal Adam, Bertrand Rozec, Michel Fuillet, Olivier Lemenand, Denis Quinsat, Ana Danalaché, Véronique Vialette, François Brosset, Patrick Messner Pellenc, Nicolas Heisel, Edouard Girard, Régine Martin, Olivier Garesslin, Catherine Mille, Alexandre Gascon, Marc Nicolino, Laurence Mouly, Claire Fabre, Bénédicte Ponceau, Marie-Etiennette Emeriau, Pascal Cathebras, Bérangère Bernardaud, Michèle Pérouse de Montclos, O. Arsene, Karine Grenet, Yazdan Yazdanpanah, Sten De Witte, Anne Scemla, Laurence Bouillet, Christophe Burucoa, Vincent Loffeier, Séverine Visentin, Luc Desfrere, Miloud Arabi, Frédérique Costa, Sylvie Lechat, Ali Chekroun, Raymond Ruimy, Marie, Jérôme Bizet, Xavier Nassif, Baihas Dib, Patrick Bert-Marcaz, Laurent Martin Lefèvre, Nicholas Sedillot, Blandine Cattier, Emilie Boidin, Daniel Sondag, Aude Bourrouillou, Alain Noirot, Franck Desemerie, Fréderic Heluwaert, Catherine Tamalet, Marc G. Berger, Jean-Daniel Lelièvre, Dominique Perotin, Abdelkader Bemrah, Alain Lozniewski, Bernard Borstein, Hanna Eid, Diana Suatean, Virginie Mignaut, Jean-Claude N'guyen, Valérie Le Goff, Laurent Teillet, Christophe Rolland, Gwenaël Alfonsi, Florence Lachenal, Philippe Bossi, Yves Botreau, Florence Doucet Populaire, Henry Jardel, Nicolas Gallo, Elias Jabre-Sikias, Michel Dupon, Hélène Brihier, Isabelle Patry, Alexandre Leclercq, Bernadette Tourrand, Christophe Roussel, Jean-Emmanuel Kurtz, Bénédicte Paindaveine, Simon Elhadad, Richard Sanchez, Eric Sgro, Pierre Berger, Valérie Murbach, Anne Holstein, Florence Martin, Taoufik Merabet, Amélie Benbara, Milagros Ferreyra, Laure Esposito, Pierre Delobel, Antoine Andremont, Marc Bourlière, Carole-Anne Boudy, Jean-Baptiste Gaulthier, Laurent Tacchini, Olivier Marpeau, Sonia Tesseydre, Marie-Pierre Coulhon, Nathalie Hodee, Marie-Chrsitine Conroy, Pierre Weinbreck, Roland Leclercq, Laurent Souply, Christian Bidault, Annie Elbez, Marie-Annick Lebreton, Patrick Brisou, Agnès Ferroni, Jean-Louis Pourriat, Nadia Anguel, Christian Noel, Philippe Jouvencel, Eric Pichard, Xavier Martin, Mathieu Coste, Pierre Zuber, Catherine Neuwirth, Jean-Pierre Hacot, Paul Aye, Jérôme Guinard, Yves Pean, Jean-Christophe Dengo, Fabrice Petassou, Didier Viole, Thierry Messiaen, Jean Beytout, Philippe Petitjean, Ferdinand Savare, Patrice Cuvillier, Sophie Coignard, Hélène Anglaret, Nassim Kamar, Elisabeth Chachaty, Karine Guimard, Louis Braem, Hacene Fezoui, Pierre Martin, Jean-Paul Viard, Claire Larroche, Nicolai Claudiu-Plesa, Thierry Benoit-Cattin, Olivier Moquet, Thierry Pasdeloup, David Rosay, Rodolphe Jean, Jean-Bernard Mariette, Marc Debouverie, Hervé Peltier, Mustapha Terki, Jacques Daleas, Valérie Dattin-Dorrière, Michel Vergnaud, Emmanuel Grimprel, Sylvène Rosselli, Jean-Marc Didier, Pierre Faurie, Luc Frimat, Aziza Mandjee, Sabine Etchemendy, Pierre Tissières, Jean Nakhleh, Sylvie Mariette, Christian Perronne, Bruno Carbonne, Nathalie Houssiaux-Maisonneuve, Tristan Ferry, S Beague, Anthony Sebban, Marie-Thérèse Hili, Jean-Michel De Kermadec, Lucien Brasme, Gilles Blaison, Caroline Garandeau, Jean-Pierre Sollet, Laurent Tronchon, Thierry Samson, Julien Gesquière, Nicolas Ettahar, Alain Créange, Etienne Laurens, Véronique Equy, Fréderic Bart, Bernard Bouffandeau, Christine Vaillant, Valerie Pesque, Jean-Marc Lalot, Marc Levy, Michel Kaidomar, Mihaela Saplacan, Sterenn Yvenou, Marie-Isabelle Steibach, Emmanuelle Cambau, Agnès Riche, François Fourrier, François Raffi, Mélissa Lalu, Henri Bérard, Danielle Clave, Jean-Claude Mouries, Martine Porcheron, Jean Cabalion, Richard Lamarca, Nathalie Canu, Jean-Baptiste Roseau, Annabelle Stoclin, Luca Luminitan Elena Lupean, Rémi Gebeile, Celia Salanoubat, Carole Marmouset, Pierre Bigot, Anne-Laure Breton, Pierre Kalfon, Colette Vincent, Sophie Marty, Olivier Tandonnet, Alexis Redor, Xavier Valette, Ourida Aoudia, Jacques-Arnaud Seyrig, Bertrand Beaune, Hugues Aumaitre, Georges Pinon, Yann Leveneur, Sylvie Charachon, Raoul Herbrecht, Henriette de Valk, Gary David, Julien Pouyanne, Marc Dommergues, Majed Al Chaar, Véronique Blanc-Amrane, Pascale Guillarmé Grossmann, Bruno Abraham, Yves Morel, Philippe Suel, Denis Sautereau, Olivier Guilloy, Tu Anh Tran, Frédéric Laurent, Zahir Amoura, Jacques-Olivier Bay, Zoubida Elharie-Heraux, Joyce Sibony-Prat, Bernard Guillois, Dominique Rohmer-Heitz, Audrey Barrelet, Jérémie Courouble, Jean-Paul Herry, Daniel Vittecoq, Annie Vermesch-Langlin, Jean Auroux, Claude Aubert, Thierry Harvey, Ghislaine Lamoine-Gimet, J. Riahi, Florence Soraudeau, Bachar Al-Jalaby, Caroline Périsson, Khélifa Ayouz, Florence Cardot, François Maillet, Alain Goux, Théophile Magna, Bertille de Barbeyrac, Adrien May, Dominique Andreotti, Olivier Jonquet, Hélène Dumouchel, Didier Thibaud, Philippe Morlat, Pascal Chevalet, Pascal Ancelin, Guy Chambreuil, Cécile Le Boterff, Anne Ceriez, Olivier Detante, B Pangon, Claude C.A. Bernard, Vincent Cailleaux Pierre-Etienne Cailleux, Jordi Miatello, Pierre-Yves le Berruyer, Sylvain Kouaho, Michel Briaud, Hélène Delaby, Patrick Herbecq, Christine Segonds, Véronique Jault, Pascale Brunel, Christine Dussopt, Jean Thore, Jean-Marc Thouret, Jean-Marc Kerleau, François Le Baron, Slavius Matica, Sophie Leautez-Nainville, Matthieu Pecquet, Laurent Bret, Yacine Sedjelmaci, Pierre Metton, Habiboulaye Diallo, Jany Rey Zermati, Arnaud Delahaye, Hélène Chaussade, Laurent Mandelbrot, Emilie Bessede, Olivier Casanovas, Paul Pierrot, Annick Legras, Dominique Lauque, Hélène Gatti, Jean Catineau, Ebutu Likose, Gilles Capellier, Eric Kibbrecht, Freddy Thibaut, Patrick Valadier, Chantal Lemble, Joël Gaudelus, Joelle Mellier, Joëlle Brochen, Emmanuel Gascou, Stéphane Bonacorsi, Stéphanie Bannier, Bruno Fantin, Didier Raffenot, Valérie Revel, Hakim Amroun, Huguette Negrery, Anne-Laure Fauchais, Paul Mercury, Michel Chuzeville, Christian Zumbo, Nicolas Després, Pascal Roblot, Jérôme Pasche, Jean Claude Boufetteau, Jocelyne Caillon, Julien Boileau, V. Rabier, Benjamin Manéglier, Emilie Jourdes, Franck Ceppa, Christine Recule, Nicolas Degand, Benoît Henry, Thierry Baranger, Dominique Pateron, Agnès Pélaquier, Gérard Bouchet, Hélène Fiette, Ozel Guiden, Dana Ranta, Etienne Ruppé, Nabil Chiouk, Jacques Breuil, Dominique Leduc, Véronique Loustaud, Hervé Métenier, Michel Durand, Isabelle Mahé, Leila Karaoui, Marie-José Collus, Mehran Monchi, Olivier Belmonte, Romain Blondet, Jacques Thierry, Karine Humbert, Gilles Salama, Marie-Noelle Heurtaux, Cécile Goujard, Bruno Sivery, Martial Boisseau, Redouane Dahoumane, Pierre Delour, Christian Niels Meyer, Anne Faudon-Gibelin, Gérard Poulain, Roger-Charles Luciani, J.-C. Souquet, Olivier Grossi, François Vandenesch, Sylvain Mermont, Jacques Bronner, Sonia Dahan, Paul Marzouk, Pascal Pouedras, Noureddine Djafari, François-Xavier Caroli-Bosc, Jean-François Dessin, Brigitte Gruffat, Armelle Morin-Fatome, Sylvie Thoinet, Bano Konate, Jean-Winoc Decousser, Claire Poyart, Patrick Plessis, Olivier Millet, Vincent Cattoir, Françoise Geffroy, Manica Vasseur, Pierre Carli, Isabelle Citony, Christian Richard, Nicolas Sigur, Patrick Marthelet, Luwawu Mbimba, Pierre Feugier, Philippe Sauder, Hama Djerad, Evelyne Bourgerette, Hanen Chahtour, Adrien Lemaignen, Dominique Bechade, Patrick Ochocki, Antoine Vieillard Baron, Dominique Astruc, Marie-Pierre Moiton, Nicolas Dubois, Sylvie Ledru, Corinne Seknazi, Hélène Poupet, Jean-Philippe Brieux, Gérard Barthélémy, Aihem Yehia, Louis-Jean Couderc, Ahmed, Françoise Rigaux, Yohann N'guyen, Philippe Bethery, Damien Corberand, Etienne Auvray, Paul-Louis Woerther, Christian Combe, Sophie Delesalle, Jean-Marie Piala, Faraj Al Freijat, Philippe Juvin, Malcolm Lemyze, Hyacine Rey, Claire Larible, Noel Milpied, Lémia Zgarni, Julia Gaillard, Agnès Juven, Paola Otean, Adrien Melis, André Pechinot, Olivier Bouchaud, Olivier Chassin, Pierre Hausfater, Asma Trabelsi-Jnifen, Vincent Grobost, Didier Lemery, Pierre Soury, Françoise Brevet, Jacques Tankovic, Dominique Sansot, Jean Louis Salomon, Charlotte Cordonnier, Brigitte Lamy, Antoine Maisonneuve, Dominique Pressac, Claude Rémy, Rodolphe Sobesky, Stéphanie Cognet, Pierre Cougoul, Didier Jan, Dominique Perrotin, Cécile Hombrouk-Alet, Thierry André, Gilbert Pochmalicki, Serge Girard, Vincent Zerr, Guillaume Cadiot, Claudine Lasbasses, Michel Slama, Abderrazak El Yamani, Sophie Brovedani, Jean Armengaud, Romain Hernu, Géraldine Mascade, Aurélien Lorléa'ch, Ali Akkari, Mathieu Tourdjman, Christopher Payan, Eric Jullian, Nathalie Fonsale, Frédéric Riehl, Paul Strock, Geneviève Grise, Philippe Mottaz, Christian Floriot, Marie-Noëlle Ungeheuer, Denis Caillot, Arnaud Chalvon-Demersay, Catherine Branger, Stanislas Bruley des Varannes, Marc Paccalin, Marie-Pierre Danjean, Alexandre Mebazaa, Xavier Brunet, Roland De Varax, Laurence Delhoustal, Sophie Haro, Bruno Chabanon-Pouget, Isabelle Goidin, Dominique Chudersky, Corinne Costes, Delphine Chatellier, Maud Gelez, Damien Dassant, Pascal Joly, Jean-Michel Arnal, Zakaria Hamitou, Philippe Rondepierre, Carole Pignon, Valérie Crombe, Amanda Lopes, Chrystelle Kemenar, Olivia Raulin, Anne-Cécile Hochart, Sandrine Gérart Pons, Valérie Zeller, Guillermo Reyes Ortega, Mathilde Guérin, Audrey Migraine Bouvagnet, Florence Eboue, Isabelle Loury-Lariviere, Sophie Leotard, Suzanne Lima, Marie Kassis, Jean-Luc Donay, Jean-Pierre Audié, Guillaume Cartron, Arnaud Ribier, Fanny Buron, Mirela Tuca, Marius Semenescu, Arnaud Serre, Vincent Quentin, Denise Bouyssou-Destriau, Violaine Bresson, Christine Chandesris Joséphine Chapalain-Cagnon, Eric Cua, Henri Courtade, François Bénézit, Sébastien Lamache, Philippe Bonnefoy, Francis Schneider, Richard Monarchi, Adeline Schendel, Paramasiven Mootien, Ghislaine Gardes, Pierre-François Westeel, Jean-François Magny, François Caron, Jocelyn Michon, Didier Eyer, Isabelle Ronda, Pierre-Yves Robillard, Frédéric Renou, Anna Faucher, Jean-Robert Harlé, Anne Debernardi, Grégory Akerman, Benoît Fontenel, Pierre Hourdebaigt-Larrusse, Marie-Noëlle Adam, Aude Lessene, Abdelkader Hrichi, François Blot, Athéna Le Pierres, Romain Lemarie, Françoise Granier, Véronique Tardy, Marc Gatfosse, Pierre-Marie Roger, François Goupil, Saïd Aberrane, Franck Bernardi, Isabelle Plantier, Nathalie Funakoshi, Jean-Gilles Delecalle, Patricia Barbut, Jacques Reynes, Christophe Roy, Sophie Perreve, Michel Garre, David Ribes, Cyrille Ede, Jean-Claude Dausset, Francis Duchene, Jean Caussin, Michelle Becker-Schneider, Gilles Berthelot, Damien Dupont, Jean-Michel Gillot, Aurélie Messager, Jean-Marie Pannecouck, Jean-Christian Roussel, Alain Reynaud, Sylvie Cariou, Anne Dao, François Guillemot, Martin Martinot, Patrick Casali, Anne-Sophie Poirier, Aissa Kerchache, Necera Sakek, Eric Porthault, Christophe Decoene, Chantal Ache-Papillon, Brigitte Bicais, Jean-Claude Feugier, Thierry Masseron, Charles Marty-Ane, Daniele Goldgran Toledano, Jean-Christophe Dubus, Damien du Cheyron, Dominique Decré, Jean-Loup Pennaforte, Ahmed Tigaizin, Bernard Vache, Eric Oswald, Claire Moulinoux, Anne-Christine Jaouen, Caroline Charlier, Anne-Laure Virlouvet, Ali Kara, Jean-Luc Sicsic, Sylvie Goffart, Mathieu Zuber, Claudine Fèbre, Olivier Lortholary, Mathieu Dupont, Annie Vessieres, Thierry Helvadjian, Thomas Signouret, Cedric Daupin, Sandrine Essouri, Jean-Louis Jacob, Pascal Boileau, Caroline Blazejewski, Quentin Lepiller, Juan-Pablo Maureira, Eddy Lebas, Christophe Deschamps, Amévi Ananivi, Clovis Foguem, Daniel Adoue, Abdourahim Chamouine, Alain Michault, Bruno Guérin, Olivier Baud, Clara Vinci, Thierry Weitten, Jean-Marc Eychene, Marie Froidure, Julien Obiols, Patricia Roussellier, Marc Lecuit, André Cabié, Saskia Foucart, Karim Belhadj, Michel Cingotti, Bruno Dumoulard, Jean Puyhardy, Etienne Danquechin Dorval, Lucile Mendes-Martin, Enrique Casalino, Luc Jarrige, Fabien Lambiotte, Philippe Masson, Mohammed Mansouria, Pierre Thouvenot, Katy Jeannot, Martine Nyunga, Valérie Macci, Florent Masia, Claire Briere de la Hosseraye, Wassila Anteur, André Sommabère, Marie-Claude Germain, Isabelle Arnault, Bernard Carbonelle, Philippe Devos, Daniel Protar, Tiphaine Gaillart, Ludovic Lassel, Laurence Hamou-Plotkine, David Trystram, Thierry Bureau, Olivier Collard, Fanny Vuotto, Sophie Malhiere, Frederique Canis, Gillles Plainfosse, Catherine Lechiche, Bertrand Lassere, Martine Chouraqui, Jean Baptiste Michot, Fethi Radhouane-Khanjari, Carole Barbier, Pascal Bonitchi, Abdelaziz Benkhelil, Odile Salmon, Laurent Damaj Gandhi, Bertrand Minguet, Michel Wagner, Odile Falguières, Zahr-Eddine Ali Chaouche, Eric Zaoui, Isabelle Guichard, Bernard Huttin, Apollinaire Karirisi, Gaël Cinquetti, Christophe Plane, Lionel Rostaing, Yanne Henry-Andrieu, Daniel Re, Virginie Verrier, Pascal Bolot, Michel De Biasi, Laurence Vrigneaud, Mathilde Turpin, Marie-Claude Demachy, Etienne Roussel, Michèle Blancs, Olivier Join-Lambert, Yves Ville, Thierry Granger, Gilles Hilbert, Virginie Medeau, Daniel Villers, Benoit Pilmis, François Gouraud, Emmanuel Ardiet, Catherine Heyraud-Blanchet, Alain Devidas, Hélène Dieye, Julie Cremniter, Jean-François Bergmann, Rozenn Le Berre, Virginie Leguen, Daniel Royer, Gilles Le Maout, Christian Harou, Sylvie Gabriel-Soléan, Yves Regouby, Martine Pestel-Caron, Patrick Brunet, David Boutoille, Emmanuelle Bonnin, Patrice Coulon, Marc Sullice, Marianne Barbieux, Gilles Cambonie, Joëlle Tricoire, Marie-Nadège Bachelier, Delphine Briend, Céline Ramanantsoa, Nathalie Bednarek, Didier Lebreton, Julien Lagrandeur, Damien M'Bey, Philippe Audeguy, Elie Saliba, Lena Damaj, Hassan Fallouh, Pascal Couturier, Fabrice Prévost, Yves Domart, Marie-Odile Lafforgue, Anne Le Du, C. Beuscart, Pierre Guillet, Fabrice Larrazet, Marie-Hélène Hausermann, Henri Robert, Nicolas Fanjaud, François Goehringer, Thomas Bachelot Philippe Badia, Jean-Michel Coulaud, Cristel Fissore Magdelein, Renaud Defebvre, Anne-Sohie Moreau, Johan Courjon, Gilles Salles, Michel Mialon, Silvia Iacobelli, Emmanuelle Bille, Marie-Christine Barbier, Yves Aubard, Patrice Badila, Jean-Philippe Rasigade, Alban Deroux, Evelyne Lecaillon-Thibon, Michel Godin, Abdelmajid Djeffal, Viorica Badurescu, Meriem Canitrot, Pierre Blanchard, Antoine Legros, Laurence Got, Françoise Duluc, Mylène M. Maury, Gilles Dassieu, Nordine Khodeir, Jean-Marie Duez, Mathieu Morincomme, Jérôme Lacroix, Mathieu Revest, Koffi Blewoussi, Isabelle Barazer, Françoise Poitevin, Camille Seignovert, Stéphanie Honore Bouakline, Anne Heidt, Brigitte Malbruny, Julien Desblache, Christian Cattoen, Eric Jaunait, Bruno Chaminade, Claude Bazin, Jonathan Chelly, Anne Pottier, Alain Schmitt, Alain Tissot, Karim Dadoun, P. Rebattu, Claudine Contamin, Arnaud Guerard, Nathalie Ravet, Sandrine Khalifa-Thellier, Marlène Chatron, Gaëlle Dörr, Hélène Biessy, Emmanuel Forestier, Bruno Devaux, Jean-Jacques Grelaud, Xavier Tchenio, Marie-Cécile Ploy, Jérémie Violette, Michèle Burdin, Lionel Falchero, Dominique Jacomy, Jean-Christophe Rozé, Damien Labarriere, Stéphane Leroux, Corinne Meregnani, Assia Ferhat Carre, Paul Orode, Jean-Gabriel Paul, Catherine Godon, Agnès Vinay, Régine Barraduc, Dominique Dallay, Alexandre Ampère, Anne-Gaelle Kervegant, Guillaume Louart, Dominique Beal Ardisson, Francoise Leonetti, Jean-Yves Baril, Stéphanie Haiat, Bincy Darre, Jérôme Bay, Yvan Gauthier, Sylvie Radenne, Pierre-Yves Gueugniaud, Philippe Ravaud, Luc Landraud, Guillaume Ranchon, Loïc Chimot, Véronique Duval, Ilhem Agha-Mir, Sabine Camiade, Estelle Wafo, Jean-Patrick Laporte, Mariam Roncato-Saberane, Camille Bron, Patrice Laudat, Samir Kennouche, Nawel Afroukh, Dominique Neri, Hakim Kherouf, Yoar Hichri, Pierre-Edouard Bollaert, Gwenaelle Vary, Denis Castaing, Christine Lefort, Sébastien Rouget, René Robert, Christelle Guillet-Caruba, Catherine Simonin, Alain Vighetto, Severine Cabasson, Alain Brusset, Alexandra Doloy, Christel Cherlet, Ahmed Rouidi, Marina Salvucci, Réginald Pordes, René-Gilles Patrigeon, Emmanuelle Dupre-Narlet, Jacques Minet, Fethi Taleb, Anne-Marie Colingorski, Tahar Hadou, Sylvain Diamantis, Isabelle Glorieux, Thierry May, Jean-Claude Colombani, Anne Berth-Farges, Nicole Desplaces, Renaud de Tayrac, Elisabeth Walter, Fabienne Lorge, Pascal Reboul, Nathalie Dournon, Laurence Estépa, Marie-Lina Toubia, Mathilde Flahault, Thierry Delacour, Dominique Hurel, Hélinoro Andriamaneo, Cécile Bébéar, Denis Grasset, Miloud Serier, Oléna Orléva, Nadine Dubroca, Hervé Gentilhomme, Jean-Luc Baudel, Isabelle Lavenu, Salim Smati, Carlo Saroufim, Eric Placidi, Albert Sotto, Benoît Libeau, Hélène Leroy, François Golfier, Christophe Dollon, Laurence Desnoulez, Eric Barre, Daniel Cohen, Pascal Priollet, Thierry Marsepoil, Benoît Lionnet, Jacques Tebib, Pascale Penn, Antoine Bouissou, Christian Roth, Olivier Martinet, Anna Schmitt, Nathalie Fruleux, Fouzia Radaoui, Jean-Marc Lessinger, Virginie Morando, Jean-Jacques Maillet, Christophe Fruchart, François Boué, François Goffinet, Franck Lellouche, Martin Demarchi, Alain Geissler, Jean-Charles Picaud, David Assouline, Patricia Brazille, Philippe Guimier, Marie-Françoise Dabysing, Bruno Delpeuch, Vanessa Tran, Guy Gengembre, Delphine Deligne, Dominique Vodovar, Yvan Touze, Sabrina Parent, Anne Decoster, Camille Dewitte, Emmanuel Weiss, Thierry Lambert, Thomas Guimard, Vincent Caille, Claude Guérin, Françoise Evreux, Geneviève Barjon, Basile Ondze, Damien Fournier, Olivia Bandin, Sophie Mignart, Henri Demontclos, Didier Perez, Jacques Croize, Nicole Desbois-Nogard, Guenièvre Imbert, Clarisse Dupin, Khalid Ridah, Marie-Christine Varin, Guillaume Arlet, Edith De Clareuil, Marie-Line Eustache, Patricia Le Pimpec, Louise Fortin, Eugène Ngami, Fabrice Mihout, Cecilia Esnault, Vincent Bouden, Véronique Annaix, Yves Poinsignon, Aurélien Lorchleac'h, Jean-Marc Degreff, Marie Garofano, Renaud Mesnage, Anne-Marie Roque-Afonso, Alain Chevailler, Stéphane Hominal, Thierry Charbonnier, Adrianna Bildea, Fabien Fily, Benjamin Davido, Emmanuel Rassiat, Assi Assi, Stéphanie Brunet, Hervé Jacquier, Catherine Claise, Annie Durand, Yannick Monceau, Pierre Blanc, Jean-Marie Sire, Yves Sucin, Jean-Pierre Zarski, Nathalie Bronet, Ingrid Lafon, Philippe Rey, Jacques Markarian, Eric Sennevile, Olivier Wink, Guilène Barnaud, Anne-Sophie Peultier, Sabine Taylor, Rim Savatier, Patrick Valayer, Claude Negrier, Selim Jennane, Edouard Begon, Laura Hyerle, Delphine Bridoux, Claire Daurel, Benoît Dalle, Mathilde Lescat, Philippe Stolidi, Elodie Perrodeau, Xavier Heches, Pierre Castelnau, Philippe Bray, Jean-Claude Texier, Serge Rossignol, Maud Brung-Lefebvre, Jean-François Subra, Jean-Marie Delarbre, Morgane Schneerson, Guyro Jang, Mona Mehri, Nathalie Landgraf, Pierre-Marie Girard, Armand Goll, Zaineb Bekguesmia, Christophe Clement, Michel Collet, Vincent Maze, Amine Benjelloul, Solène Durliat-Ellie, Vincent Letouzey, François Schmitt, Valérie Martinez, Sarah Watson, Abderrezak Bouasria, François Barbier, Raphael Lauretta, Mirana Razafimahery, Cristina Sirbu, Patrick Malherbe, Anne Wuillai, Ludovic Lesecq, Philippe Gaudard, Serge Houssaye, Jacques Monsegu, Gilles Rival, Chantal Chaplain, Jean-Didier Grangé, Oana Zamfiri, Florence Nguyen-Khac, Marc Portneuf, Jean-Michel Pawlotsky, Delphine Bonnet, Laurent Traissac, Sophie Hamon-Charles, Didier Dreyfuss, Louis Bernard, Laurence Detourmignies, Olivier Martineau, François Pettinelli, Marc Zandecki, Michel Dreyfus, Alain Chapelle, Sébastien Sabbat, Anne-Sophie Labussiere, Jean-Louis Gaillard, Chloé Plouzeau-Jayle, Patrick Zoveda, Véronique Leflon, Marie Levy, Aurélie Labé, Bruno Soulie, Raoul Jacques Bensaude, Hecham Moussa, Sylviane Catteu, Nathalie Biron, Loïc Masson, Georges Mourad, Nejla Aissa, Dragos Ciocan, Hubert De Boysson, Jean-Luc Bouyer, Patrick Yeni, Thierry-Pascal Zame, Caroline Thomas, François Cavalié, Laurence Koulmann, Christophe Rioux, Olivier Barraud, François Bricaire, Marguerite Le Poulain, Marie-Noelle Noulard, René Thomas, Guy Semet, Laurent Mosser, Olivier Marret, Brigitte Rivière, Vincent Jarlier, Jean-Philippe Coindre, Marc Villemain, Martin Pierre, Yacine Benkaci, Philippe Chiron, Hoang Vu-Thien, Jérôme Gournay, Andrea Labaune-Kiss, Brigitte Lauzanne, Fanny Lemercier, Souad Silhadi, Imad Kansau, Christophe Poncelet, Olivier Baldesi, Francis Thuet, Olivier Leroy, Aurore Lamberet, Camille Petit Hoang, Sophie Micheli, Ayman Abokasem, Hakima Nesrine, Pierre Lureau, Christian Chidiac, Vincent Piriou, Fabien Zoulim, Dieudonné Nicobaharaye, Anne Tixier, Isabelle Matheron, Soumeth Abasse, Victoria Cacheux, Serge Herson, Christine Fuhrmann, Olivier Proost, Bernard Bedock, Olivier Rogeaux, Mostapha Hajjar, Anne Reverseau, René Courcol, Françoise Carmagnol, Yves Guénard, Céline Ménard, Bouchra Lamia, Bruno Lemmens, Damien Bouhour, L. Lequen, Gaëlle Baty, Cédric Bouet, Dominique Guerrot, Stéphane Blanc, Catherine Chirouze, Anne-Hélène Reboux, A. Vachée, Gregory Taurin, Myriam Mein-Bottini, Jean-Pierre Belot, Alain Lafeuillade, Patricia Gabez-Therou, Philippe Labrousse, Bernard Jarrousse, Philippe Noto, Vincent Brunot, Philippe Condominas, Marion Challier, Béatrice Berçot, Delphine Anuset, Mélanie Daval Cote, François Bernasconi, Y. Costa, Chandrah Goburdhun, Bernard Gressier, Alban Michaud-herbst, Franck Charlier, Moussa Hecham, Luc Boulain, Hélène Corneloup, Alix Greder Belan, Nicolas Boussekey, Claire-Antoinette Dupuy, Yannick Rouquet, Benoit Renard, Benifla Jl, Etienne Javouhey, Michèle Granier, Marie-Christine Jaffarbandjee, Emilie Piet, Benoît Bergues, Claire Malbrunot, Catherine Tiry, Philippe Mérigot, Mouna Ben Soltana, Chantal Roure Sobas, Florian Radenac, Yves Thomas, Agathe Blaise, Sylvie De Martino, Laurence Legout, Gabriel Choukroun, Jean-François Muir, Peggy Dupretz, Patrick Dupont, François Guichart, Julie Jean, Jean-Michel Descamps, Bernard Kittschke, Anne Gruson, Gerard Viquesnel, Marie Keller, Pascal Chavanet, Françis Vallet, Yvan Vaschalde, Jean-Luc Hanouz, Gerard Lina, Françoise Loison, Simon Vincent, Jean-Paul Thellier, Moncef Afi, Dominique Zagozda, Hélène Sokeng-Affoule, Marc Le Bideau, Jean-François Loriferne, Alain Gravet, Sophie Deprecq, Tarik Naceur, Severine Mielczarek, René-Jean Bensadoun, Bernard Karkous, Yves Bléher, Jocelyne Poulain, Véronique Goulet, Laurence Nicolet, Sophie Arista, Antônio Lúcio Teixeira, Jean-François Schved, Laurent Nicolet, Claire Lecomte, Faiza Benddif-Fin, Michel Aumersier, Laurence Burc-Struxiano, Maxime Thouvenin, Samia Harbi, Mathieu Detave, Catherine Rebeyrotte, Jean-Paul Kisterman, Bruno Berdin, Pascal Vincent, Laurent Argaud, Elisabeth Parisi-Duchene, Geneviève Julienne, Fernanda Farto-Bensasson, Georges-Fabrice Blum, Sad Gaizi, Tali-Anne Szwebel, Raphaël Lepeule, Marie-Thérèse Climas, Anne-Françoise Dillies, Amar Boudhane, Umberto Simeoni, Pierre-François Dequin, Gérard Oliviero, Alain Gourlaouen, Caroline Piau, Marie-France Lutz-Murphy, Benoît Claude, Jean-Paul Aubry, Nadine Dubosc-Marchenay, Kamilla Chraibi, Emmanuelle Heusse, Sylvain Le Chevallier, Nathalie Brieu, Farid Sifaoui, Lorraine Letranchant, Hélène Durox, Jean-Pierre Lagasse, Adel Ghedira, Xavier Roubert, Fatma Magdoud, Hélène Jean-Pierre, Etienne Carbonelle, Olivier Dereeper, Lionel Carbillon, Christophe Billy, Mélanie Roblin, Marie-José Kodzin, Philippe Niel, Solène Makdessi, Matteo Vassallo, Maryse Archambaud, Fabian Haccourt, Didier Blaise, Stéphane Bourgeois, Elena Marcu, Charles Kubiak, Brisse Castel, François Guinet, Marie Pouzoullic, Frédérique Nathan-Bonnet, Vincent Gendrin, Céline Becherrawy, Aline Secher, Pierre Abgueguen, Clarence Eloy, Jean-Marc Tourani, Frédéric Klapczynski, Bernard Montmasson, Philippe Real, Joanna Pofelski, Yves Welker, Karim Krechiem, Eric Caumes, Martine Elena-Daumas, Christophe Saigne, Gilles Hittinger, Chantal Delesalle, Jonathan Messika, Fabrice Lesage, Daniela Pop, Daniel Coetmeur, Renato Colamarino, Chetaou Mahaza, Patrick Plésiat, Isabelle Fredenucci, Mylène Baret, Guy Mager, Pascale Chavel, Isabelle Labourdette, Anne-Claude Menguy, Nicolas Fortineau, Ludovic Le Sec, Valérie Gauduchon, Francis Barraud, Nicolas Letellier, Didier Vincent, Janine Frey, Philippe Riegel, Michel Pavic, Jean-Luc Fabre, Jean-Pierre Fauchart, Alain Goudeau, Stéphanie Husson-Wetzel, Philippe Eymerit, Mohamed Camara, Nathalie Seta, Elisabeth Carole Ngo Bell, Philippe Repellin, Laurent Alric, Vincent Leroy, Françoise Delisle Mizon, Jean-Philippe Emond, Marie-Françoise Borie, Lise Crémet, Wladimir Chelle, Elisabeth Brottier-Mancini, Bernard Garrigues, Claire Letellier, Loïc Geffray, Frédéric Méchaï, Julien Bador, Benoit Guery, Alain-Charles Fouilhoux, Corinne Dagada, Pierre Duhaut, Julien Goustille, Arnaud Sément, Francis Carcenac, Isabelle Girard-Buttaz, Claire Chapuzet, Fabienne Jouatte, Bruno Riou, Fabrice Hayoun, Chloé Di Meglio, Youssef Ali, Michel Leneveu, Nathalie Montagne, Yves Garcera, Audrey Moustache, Pierre-Eric Danin, Geneviève Le Lay, Dominique Courouge-Dorcier, Isabelle Worcel, Emmanuel Morelon, Vincent Pestre, Jean-Pierre Vilque, Jean-Christophe Paquet, Lucien Bodson, Anne-Marie Forest, Fabrice Pierre, Christian Pommier, Fabien Dutasta, Pierre Fournel, Stéphanie Courtois, Elodie Dubois, Serge Vanden Einjden, Patrick Honderlick, Pascal Richette, Fabienne Tamion, Véronique Chassy, Richard Megbemado, Anne-Marie Le Reste, Bernard Simian, Henri Osman, Anthony Texier, Badih Ayach, François Simon, Jean-Michel Filloux, Béatrice Dubourdieu, Jean-Claude Semet, Sarah Kubab, Tawfiq Henni, Patrick Dudeffant, Delphine Hequet, Olivier Mimoz, Marc Auburtin, Amélie Chabrol, Mickael Bonnan, Caroline Léonnet, Claire Wintenberger, Serge Ilunga, Patrice Lanba, Sophie Rosello, Alexandre Damage, Flore Bouche, Michel Thibault, Frederic Faibis, Chantal Dhennain, Jean-Philippe Talarmin, Armelle Lamour, Remi Boussier, Fabien Garnier, Marie-Laure Brival, Nourredine Hedjem, Philippe Vande-perre, Raphaël Coint, Jean-Claude Reveil, Eva Weinbronn, Emmanuelle Lavalard, Alexandra Fille, Françoise Le Turdu, Lionel Leroux, Jean-Yves Lefrant, Jean Berthet, Radia Bouaziz, Alain Ravaud, Sylvaine Rousseau, Yacine Merrouche, Alain Le Coustumier, Bertrand Guider, Gisèle Dewulf, Jean-Marc Faucheux, Jacques Piquet, Franck Leibinger, Charles Cerf, Robin Stephan, Jean-Philippe Redonnet, Jean-Paul Stahl, Ella Dzeing, Simona Pavel, Guy Vernet, Ghada Hatem, Samer Kayal, Jacques Deschamps, Dominique Descamps, Marion Levast, Marc Bouiller, Sylvie Dargere, Claire Dingremont, Stéphane Gaudry, François Maillot, Sylvie Odent, Nathalie Cervantes, Hélène Zanaldi, Laurence Gachassin, Olivier Ruyer, David Patin, Benoît Cazenave, Pascal Jacquier, Michelle Boyer, Béatrice Berteaux, Virginie Zarrouk, Jacques Bor, Isabelle Legoff, Hélène Albinet, Florence Rousseau, Gilles Pialoux, Guenaelle Salaun-Beretta, Alexandra Moura, Véronique Vernet Garnier, Didier Lepelletier, Pierre-Alexandre Hauss, Joëlle Belaisch-Amart, Didier Lepeletier, Jacob Xavier, Aline Nare, Annie Motard-Picheloup, Alain Améri, Bertrand Lioger, Jean-Valère Malfuson, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, MONALISA study group, Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., ROZIER, marie-Claire, CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections ( CNRL ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre collaborateur de l'OMS (CCOMS) des Listeria ( CCOMS ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Lariboisière, Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Agence Nationale de la Santé Publique [Saint-Maurice] ( ANSP ), Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Bacteremia/epidemiology/mortality, 0301 basic medicine, Male, Pediatrics, bacteraemia, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], Bacteremia, France/epidemiology, Infant, Newborn, Diseases, Foodborne Diseases, Meningoencephalitis, Pregnancy, Risk Factors, Vertical, Medicine, Listeriosis, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, ddc:618, diabetes, alcoholism, Hazard ratio, Foodborne Diseases/microbiology, immuno suppressive therapies, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, isolates, Population Surveillance, Female, France, Listeria monocytogenes/classification/isolation & purification, Cohort study, Adult, medicine.medical_specialty, 030106 microbiology, Notifiable disease, Listeriosis/diagnosis/epidemiology/microbiology, Context (language use), macromolecular substances, 03 medical and health sciences, Humans, study, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Public health, cirrhosis, Infant, Newborn, Infant, Diseases/epidemiology/microbiology, HIV, Mandatory Reporting, Newborn, medicine.disease, Listeria monocytogenes, infection, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious/epidemiology/microbiology, Meningoencephalitis/epidemiology/microbiology/mortality, Observational study, business, prognostic, mellitus
Abstract: International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (
Published: 2016
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25. 0215 : Is Transient Receptor Potential Vanilloid Type 1 (TRPV1) a target of isoflurane in cardiomyocytes?

Author: S. Bidault-Ducreux, Lionel Augeul, L. Païta, Christophe Chouabe, R. Bonvallet, F. Van Coppenolle, R. Al-Mawla, Michel Ovize, S. Dupré-Aucouturier, and Annie Durand
Subjects: Sarcolemma, business.industry, musculoskeletal, neural, and ocular physiology, TRPV1, chemistry.chemical_element, Skeletal muscle, Calcium, Calcium in biology, Cell biology, Transient receptor potential channel, medicine.anatomical_structure, chemistry, Anesthesia, medicine, lipids (amino acids, peptides, and proteins), business, Cardiology and Cardiovascular Medicine, Intracellular, Homeostasis
Abstract: During a myocardial infarct, oxygen and nutrients deprivation triggers a reticular stress disrupting the Ca2+ balance of the cardiac cell. Several Ca2+ pumps and channels located at the sarcolemma or at the reticulum membrane are key players in this maintenance of Ca2+ homeostasis. Among them, we find passive leak channels, such as TRPs. Their involvement in myocardial ischemia-reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. TRPV1 represents a non-selective cation channel that is activated by capsaicin, pH and high temperature. In skeletal muscle, we recently demonstrated that TRPV1 is located in the longitudinal part of the SR and respond to pharmacological and physiological activations (Lotteau et al., 2013). We questioned here whether TRPV1 might have a role in heart physiology. Biochemical analysis and intracellular Ca2+ measurements were performed on cardiomyocytes from wild-type and TRPV1-KO mice. Our in vitro results show that: (i) TRPV1 is expressed in cardiac cells; (ii) an increase in intracellular calcium concentration ([Ca2+]i) is elicited under TRPV1 activation; (iii) TRPV1 could be a direct target of isoflurane. In parallel, our in vivo results indicate that a pharmacological preconditioning by isoflurane decrease the infarct size, probably though activation of TRPV1. Ca2+ is central for the heart function, through its physiological role in excitation- contraction coupling, and the detrimental impact of Ca2+ overload during myocardial ischemia-reperfusion. It appears crucial to clarify the role of calcium leak channels such as TRPV1 channels in regulating Ca2+ homeostasis. According to the fact that TRPV1 activity can be modulated by a lot of pharmacological molecules, TRPV1 may serve as therapeutic target to reduce the infarct size. The author hereby declares no conflict of interest
Published: 2016
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26. Inside front cover: Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice

Author: Gaëlle Pineau, Carole Vaysse, Leslie Couëdelo, Alain Géloën, Armelle Penhoat, Emmanuelle Meugnier, Pascale Plaisancié, Laure Gabert, Florent Joffre, Manon Lecomte, Bérengère Benoit, Marion Létisse, Annie Durand, Marie-Caroline Michalski, and Fabienne Laugerette
Subjects: 0404 agricultural biotechnology, Front cover, Chemistry, medicine, Inflammation, 04 agricultural and veterinary sciences, Food science, medicine.symptom, 040401 food science, High fat fed, Food Science, Biotechnology
Published: 2016
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27. Disruption of calcium transfer from ER to mitochondria links alterations of mitochondria-associated ER membrane integrity to hepatic insulin resistance

Author: Maud Michelet, Amélie Bravard, Alain Lacampagne, Guillaume Vial, Hubert Vidal, Marie-Agnès Chauvin, Annie Durand, Elise Belaidi, Melanie Paillard, Pierre Theurey, Jennifer Rieusset, Marie Demion, Jérémy Fauconnier, Emily Tubbs, Fabien Zoulim, Geoffrey Teixeira, Emilie Blond, Birke Bartosch, Michel Ovize, Ludovic Gomez, 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations Fonctionnelles Cardiovasculaires (SEFC), Hospices Civils de Lyon (HCL), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie moléculaire et nouveaux traitements des hépatites virales, Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardioprotection, Université de Lyon-Université de Lyon-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), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Mitochondrion, Biology, Cell Line, Cyclophilins, Mice, 03 medical and health sciences, Insulin resistance, 5-triphosphate receptor, Internal Medicine, medicine, Mitochondria-associated endoplasmic reticulum membranes, Animals, Humans, Inositol 1,4,5-Trisphosphate Receptors, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Protein kinase C, Calcium signaling, Mice, Knockout, PKCε, Endoplasmic reticulum, Insulin, Calcium signalling, STIM1, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Inositol 1, Cell biology, Mitochondria, 030104 developmental biology, Liver, Inositol 1 4 5-triphosphate receptor, Hepatocytes, Unfolded protein response, Calcium, Cyclophilin D
Abstract: Mitochondria-associated endoplasmic reticulum membranes (MAMs) are regions of the endoplasmic reticulum (ER) tethered to mitochondria and controlling calcium (Ca(2+)) transfer between both organelles through the complex formed between the voltage-dependent anion channel, glucose-regulated protein 75 and inositol 1,4,5-triphosphate receptor (IP3R). We recently identified cyclophilin D (CYPD) as a new partner of this complex and demonstrated a new role for MAMs in the control of insulin's action in the liver. Here, we report on the mechanisms by which disruption of MAM integrity induces hepatic insulin resistance in CypD (also known as Ppif)-knockout (KO) mice.We used either in vitro pharmacological and genetic inhibition of CYPD in HuH7 cells or in vivo loss of CYPD in mice to investigate ER-mitochondria interactions, inter-organelle Ca(2+) exchange, organelle homeostasis and insulin action.Pharmacological and genetic inhibition of CYPD concomitantly reduced ER-mitochondria interactions, inhibited inter-organelle Ca(2+) exchange, induced ER stress and altered insulin signalling in HuH7 cells. In addition, histamine-stimulated Ca(2+) transfer from ER to mitochondria was blunted in isolated hepatocytes of CypD-KO mice and this was associated with an increase in ER calcium store. Interestingly, disruption of inter-organelle Ca(2+) transfer was associated with ER stress, mitochondrial dysfunction, lipid accumulation, activation of c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)ε and insulin resistance in liver of CypD-KO mice. Finally, CYPD-related alterations of insulin signalling were mediated by activation of PKCε rather than JNK in HuH7 cells.Disruption of IP3R-mediated Ca(2+) signalling in the liver of CypD-KO mice leads to hepatic insulin resistance through disruption of organelle interaction and function, increase in lipid accumulation and activation of PKCε. Modulation of ER-mitochondria Ca(2+) exchange may thus provide an exciting new avenue for treating hepatic insulin resistance.
Published: 2016
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28. Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice

Author: Annie Durand, Carole Vaysse, Marion Létisse, Pascale Plaisancié, Gaëlle Pineau, Armelle Penhoat, Alain Géloën, Marie-Caroline Michalski, Florent Joffre, Manon Lecomte, Fabienne Laugerette, Leslie Couëdelo, Laure Gabert, Emmanuelle Meugnier, Bérengère Benoit, 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), Region Rhone-Alpes ARC1, Lipides pour l'Industrie et la Sante, Societe Francophone du Diabete, 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 des Corps Gras (ITERG), 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), 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 (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), Université Panthéon-Sorbonne - UFR d'Économie (UP1 UFR02), Université Panthéon-Sorbonne (UP1), ITERG (ITERG), ITERG, Régulations métaboliques, nutrition et diabètes (RMND), Oméga 21, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Panniculitis, [SDV]Life Sciences [q-bio], Adipose tissue, Metabolic disease, White adipose tissue, chemistry.chemical_compound, Feces, Intestinal mucosa, Gut barrier, Lecithins, Diet, Fat-Restricted, ComputingMilieux_MISCELLANEOUS, Adiposity, 2. Zero hunger, chemistry.chemical_classification, Leptin, Lipids, 3. Good health, Phospholipid, Milk, Liver, Tumor necrosis factor alpha, Goblet Cells, medicine.symptom, Biotechnology, medicine.medical_specialty, Colon, Adipose Tissue, White, Inflammation, Biology, Diet, High-Fat, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, 030109 nutrition & dietetics, Fatty acid, Caco-2, Mice, Inbred C57BL, Endocrinology, chemistry, Emulsifying Agents, Immunology, Soybeans, Caco-2 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; SCOPE: Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. METHODS AND RESULTS: Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p \textless 0.05), with larger adipocytes (p \textless 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p \textless 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p \textless 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p \textless 0.05), and more goblet cells in the colon (p \textless 0.05). CONCLUSIONS: Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak.
Published: 2016
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29. The SR/ER-mitochondria calcium crosstalk is regulated by GSK3beta during reperfusion injury

Author: Maryline Abrial, Michel Ovize, S-S Sheu, F. Van Coppenolle, Melanie Paillard, L Gomez, Annie Durand, P-A Thiebaut, C. Crola Da Silva, Muhammad Rizwan Alam, Sylvie Ducreux, 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), 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Programmed cell death, [SDV]Life Sciences [q-bio], Myocardial Reperfusion Injury, macromolecular substances, Mitochondrion, Bioinformatics, Mitochondria, Heart, Cell Line, 03 medical and health sciences, Glycogen Synthase Kinase 3, 0302 clinical medicine, Medicine, Animals, Inositol 1,4,5-Trisphosphate Receptors, Myocytes, Cardiac, Calcium Signaling, Phosphorylation, Molecular Biology, Heart metabolism, 030304 developmental biology, Calcium signaling, 0303 health sciences, Original Paper, Glycogen Synthase Kinase 3 beta, business.industry, Endoplasmic reticulum, Myocardium, Cell Biology, medicine.disease, Cell biology, Mice, Inbred C57BL, Cytosol, Sarcoplasmic Reticulum, Apoptosis, Calcium, business, Corrigendum, Reperfusion injury, Protein Processing, Post-Translational, 030217 neurology & neurosurgery
Abstract: International audience; Glycogen synthase kinase-3beta (GSK3beta) is a multifunctional kinase whose inhibition is known to limit myocardial ischemia-reperfusion injury. However, the mechanism mediating this beneficial effect still remains unclear. Mitochondria and sarco/endoplasmic reticulum (SR/ER) are key players in cell death signaling. Their involvement in myocardial ischemia-reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. We questioned here whether GSK3beta might have a role in the Ca(2+) transfer from SR/ER to mitochondria at reperfusion. We showed that a fraction of GSK3beta protein is localized to the SR/ER and mitochondria-associated ER membranes (MAMs) in the heart, and that GSK3beta specifically interacted with the inositol 1,4,5-trisphosphate receptors (IP3Rs) Ca(2+) channeling complex in MAMs. We demonstrated that both pharmacological and genetic inhibition of GSK3beta decreased protein interaction of IP3R with the Ca(2+) channeling complex, impaired SR/ER Ca(2+) release and reduced the histamine-stimulated Ca(2+) exchange between SR/ER and mitochondria in cardiomyocytes. During hypoxia reoxygenation, cell death is associated with an increase of GSK3beta activity and IP3R phosphorylation, which leads to enhanced transfer of Ca(2+) from SR/ER to mitochondria. Inhibition of GSK3beta at reperfusion reduced both IP3R phosphorylation and SR/ER Ca(2+) release, which consequently diminished both cytosolic and mitochondrial Ca(2+) concentrations, as well as sensitivity to apoptosis. We conclude that inhibition of GSK3beta at reperfusion diminishes Ca(2+) leak from IP3R at MAMs in the heart, which limits both cytosolic and mitochondrial Ca(2+) overload and subsequent cell death.
Published: 2016
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30. Reduction of endoplasmic reticulum stress using chemical chaperones or Grp78 overexpression does not protect muscle cells from palmitate-induced insulin resistance

Author: Marie-Agnès Chauvin, Marie-Caroline Michalski, Jennifer Rieusset, Hubert Vidal, Fabienne Laugerette, Annie Durand, Amélie Bravard, 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: Male, medicine.medical_treatment, Muscle Fibers, Skeletal, Palmitates, Adipose tissue, MESH: Heat-Shock Proteins, Biochemistry, Mice, 0302 clinical medicine, MESH: Endoplasmic Reticulum Stress, Insulin, Myocyte, MESH: Animals, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, 0303 health sciences, MESH: Muscle Fibers, Skeletal, biology, Tunicamycin, Endoplasmic Reticulum Stress, MESH: Insulin Resistance, medicine.anatomical_structure, MESH: Dietary Fats, medicine.medical_specialty, Biophysics, 030209 endocrinology & metabolism, MESH: Insulin, Butylamines, Taurochenodeoxycholic Acid, 03 medical and health sciences, Insulin resistance, MESH: Diet, MESH: Mice, Inbred C57BL, Internal medicine, medicine, MESH: Butylamines, MESH: Taurochenodeoxycholic Acid, Animals, MESH: Mice, Molecular Biology, 030304 developmental biology, MESH: Tunicamycin, Endoplasmic reticulum, Skeletal muscle, Cell Biology, MESH: Palmitates, medicine.disease, Dietary Fats, MESH: Male, Diet, Mice, Inbred C57BL, Insulin receptor, Endocrinology, biology.protein, Unfolded protein response, Insulin Resistance, [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
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31. Dynamic regulation of mitochondrial network and oxidative functions during 3T3-L1 fat cell differentiation

Author: Mireille Weitheimer, Annie Durand, Mélissa Flamment, Lucie Duluc, Jennifer Rieusset, Mélanie Priou, Gilles Simard, Yves Malthièry, Pierre-Henri Ducluzeau, Raffaela Soleti, Ramaroson Andriantsitohaina, Fransceco Iacobazi, Université d'Angers (UA), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon
Subjects: STRESS, Physiology, [SDV]Life Sciences [q-bio], Gene Expression, Mitochondrion, Biochemistry, Mice, 0302 clinical medicine, Lipid droplet, Adipocytes, TRANSCRIPTION, NRF1, Membrane Potential, Mitochondrial, 0303 health sciences, Adipogenesis, Microscopy, Video, Cell Differentiation, General Medicine, Catalase, Mitochondria, ADIPOSE-TISSUE, OBESITY, OXYGEN SPECIES PRODUCTION, Adiponectin, Oxidation-Reduction, BIOGENESIS, Citrate (si)-Synthase, Oxidative phosphorylation, Biology, Nitric Oxide, Electron Transport Complex IV, Mitochondrial Proteins, 03 medical and health sciences, Oxygen Consumption, Lipid oxidation, 3T3-L1 Cells, Animals, Enzyme Assays, 030304 developmental biology, Mitochondrial network, Glutathione Peroxidase, NITRIC-OXIDE, L-Lactate Dehydrogenase, Superoxide Dismutase, TFAM, Fat cell differentiation, DYSFUNCTION, Lipid metabolism, Fatty Acid Synthases, Reactive Oxygen Species, 030217 neurology & neurosurgery
Abstract: International audience; Mitochondria have been shown to be impaired in insulin resistance-related diseases but have not been extensively studied during the first steps of adipose cell development. This study was designed to determine the sequence of changes of the mitochondrial network and function during the first days of adipogenesis. 3T3-L1 preadipocytes were differentiated into adipocytes without using glitazone compounds. At days 0, 3, 6, 9, and 12, mitochondrial network imaging, mitochondrial oxygen consumption, membrane potential, and oxidative phosphorylation efficiency were assessed in permeabilized cells. Gene and protein expressions related to fatty acid metabolism and mitochondrial network were also determined. Compared to preadipocytes (day 0), new adipocytes (days 6 and 9) displayed profound changes of their mitochondrial network that underwent fragmentation and redistribution around lipid droplets. Drp1 and mitofusin 2 displayed a progressive increase in their gene expression and protein content during the first 9 days of differentiation. In parallel with the mitochondrial network redistribution, mitochondria switched to uncoupled respiration with a tendency towards decreased membrane potential, with no variation of mtTFA and NRF1 gene expression. The expression of PGC1 alpha and NRF2 genes and genes involved in lipid oxidation (UCP2, CD36, and CPT1) was increased. Reactive oxygen species (ROS) production displayed a nadir at day 6 with a concomitant increase in antioxidant enzyme gene expression. This 3T3-L1-based in vitro model of adipogenesis showed that mitochondria adapted to the increased number of lipid droplets by network redistribution and uncoupling respiration. The timing and regulation of lipid oxidation-associated ROS production appeared to play an important role in these changes.
Published: 2011
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32. Imeglimin Normalizes Glucose Tolerance and Insulin Sensitivity and Improves Mitochondrial Function in Liver of a High-Fat, High-Sucrose Diet Mice Model

Author: Hubert Vidal, Jennifer Rieusset, Nadia Bendridi, Guillaume Vial, Jean-Paul Pais de Barros, Cécile Acquaviva, Eric Fontaine, Annie Durand, Sophie Hallakou-Bozec, Sébastien Bolze, Anne-Marie Madec, Marie-Agnès Chauvin, Nathalie Bernoud-Hubac, Emmanuelle Meugnier, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), 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), Plateforme Lipidomique [Dijon] (LAP), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), NEANT, neant, Service de Maladies Héréditaires du Métabolisme, Centre de Biologie Et de Pathologie Est - Bron Centre médical, 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 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), meugnier, emmanuelle, Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
Subjects: Male, medicine.medical_specialty, Male, Animals, Mice, Inbred C57BL, Insulin Resistance/*physiology, Diet, High-Fat/adverse effects, Hypoglycemic Agents/*therapeutic use, Liver/*drug effects/*metabolism, Mitochondria/*drug effects/*metabolism, Triazines/*therapeutic use, Imeglimin, Mitochondria/*drug effects/*metabolism, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], High-Fat/adverse effects, Biology, Mitochondrion, Diet, High-Fat, medicine.disease_cause, Inbred C57BL, chemistry.chemical_compound, Mice, Lipid oxidation, Internal medicine, Internal Medicine, medicine, Hypoglycemic Agents/*therapeutic use, Hypoglycemic Agents, Animals, Protein kinase B, Beta oxidation, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Reactive oxygen species, Triazines/*therapeutic use, Triazines, Mitochondria, 3. Good health, Diet, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Endocrinology, Liver/*drug effects/*metabolism, Liver, chemistry, Insulin Resistance/*physiology, Coenzyme Q – cytochrome c reductase, Insulin Resistance, Oxidative stress
Abstract: International audience; Imeglimin is the first in a new class of oral glucose-lowering agents currently in phase 2b development. Although imeglimin improves insulin sensitivity in humans, the molecular mechanisms are unknown. This study used a model of 16-week high-fat, high-sucrose diet (HFHSD) mice to characterize its antidiabetic effects. Six-week imeglimin treatment significantly decreased glycemia, restored normal glucose tolerance, and improved insulin sensitivity without modifying organs, body weights, and food intake. This was associated with an increase in insulin-stimulated protein kinase B phosphorylation in the liver and muscle. In liver mitochondria, imeglimin redirects substrate flows in favor of complex II, as illustrated by increased respiration with succinate and by the restoration of respiration with glutamate/malate back to control levels. In addition, imeglimin inhibits complex I and restores complex III activities, suggesting an increase in fatty acid oxidation, which is supported by an increase in hepatic 3-hydroxyacetyl-CoA dehydrogenase activity and acylcarnitine profile and the reduction of liver steatosis. Imeglimin also reduces reactive oxygen species production and increases mitochondrial DNA. Finally, imeglimin effects on mitochondrial phospholipid composition could participate in the benefit of imeglimin on mitochondrial function. In conclusion, imeglimin normalizes glucose tolerance and insulin sensitivity by preserving mitochondrial function from oxidative stress and favoring lipid oxidation in liver of HFHSD mice.
Published: 2015
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33. [PP.16.03] IS TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE 1 (TRPV1) A NEW TARGET FOR CARDIOPROTECTION?

Author: S. Dupré-Aucouturier, R. Al-Mawla, R. Bonvallet, Lionel Augeul, F. Van Coppenolle, Annie Durand, L. Paita, Michel Ovize, S. Bidault-Ducreux, and C. Chouabe
Subjects: Cardioprotection, Transient receptor potential channel, Physiology, business.industry, Internal Medicine, TRPV1, Medicine, Pharmacology, Cardiology and Cardiovascular Medicine, business
Published: 2016
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34. α4 Integrins and L-selectin Differently Orchestrate T-cell Activity During Diabetes Prevention Following Oral Administration of CTB-insulin

Author: Annie Durand, A. Stefanutti, Charles Thivolet, Caroline Aspord, and Cecil Czerkinsky
Subjects: CD4-Positive T-Lymphocytes, Male, Cholera Toxin, medicine.medical_specialty, Integrin alpha4, T-Lymphocytes, medicine.medical_treatment, T cell, Immunology, Spleen, medicine.disease_cause, Autoimmunity, Immune tolerance, Mice, Adjuvants, Immunologic, Mice, Inbred NOD, Internal medicine, medicine, Animals, Hypoglycemic Agents, Insulin, Immunology and Allergy, L-Selectin, biology, Pancreatic islets, Cholera toxin, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Endocrinology, biology.protein, Female, L-selectin, Cell Adhesion Molecules
Abstract: Oral administration of insulin conjugated to the B chain of cholera toxin (CTB-insulin) in non-obese diabetic (NOD) mice results in diabetes prevention. We investigated the respective contributions of L-selectin (CD62L) and alpha4-integrin pathways during CTB-driven tolerance. Purified CD62L+CD4+ cells from CTB-insulin fed mice significantly reduced the capacity of diabetogenic T cells to transfer diabetes in syngeneic recipients. In vivo antibody blockade of fed animals during adoptive co-transfer experiments indicated that both CD62L and alpha4-integrins pathways were necessary to develop a protective response after oral tolerance induction. In contrast, when antibodies were given to recipient mice, only CD62L was critical for the protection. In vitro stimulated CD62L+CD4+ cells from the spleen of fed animals secreted lower amounts of IL-4 and IL-10 but comparable levels of TGFbeta than CD62L-cells. A reduced IFN-gamma production between the two cell subsets was specifically observed in CTB-insulin fed mice. Furthermore, antibody treatments induced changes in T-cell migration to the spleen, mesenteric and pancreatic lymph nodes. The protective effect was also associated with migration of regulatory T cells into pancreatic islets. Taken together, our results suggest that L-selectin and alpha4-integrin have distinct but complementary roles in the generation and function of regulatory CD4+ T cells following CTB-insulin administration.
Published: 2002
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35. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans

Author: Amélie Bravard, Jennifer Rieusset, Jingwei-Ji Cao, Etienne Lefai, Hubert Vidal, Annie Durand, David Patsouris, Fabienne Laugerette, Marie-Agnès Chauvin, Martine Laville, Christine Durand, Guillaume Vial, Marie-Caroline Michalski, Cyrille Debard, 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 Patsouris, David
Subjects: Male, Chemokine, Muscle Physiology, Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Skeletal/*immunology/metabolism/pathology"*"Myositis/*immunology/metabolism, Mice, Obese, lcsh:Medicine, White adipose tissue, chémokine, Cell Movement, Immune Physiology, lcsh:Science, Immune Response, Chemokine CCL2, Obese"*"Mice, Innate Immune System, Multidisciplinary, biology, Myogenesis, muscle squelettique, medicine.anatomical_structure, Endocrinologie et métabolisme, Tumor necrosis factor alpha, medicine.symptom, Research Article, medicine.medical_specialty, diabète de type 2, Immunology, Inflammation, Mice, Transgenic, macrophage, Cell Line, Insulin resistance, Internal medicine, medicine, Animals, Humans, Transgenic"*"Muscle, Muscle, Skeletal, résistance à l'insuline, Nutrition, Endocrinology and metabolism, Endocrine Physiology, Myositis, Insulin, Macrophages, lcsh:R, Skeletal muscle, Biology and Life Sciences, Animals"*"Cell Line"*"Cell Movement"*"Chemokine CCL2/*physiology"*"Diabetes Mellitus, Nutrients, Type 2/immunology/metabolism"*"Humans"*"Insulin Resistance/*immunology"*"Macrophages/*immunology"*"Male"*"Mice, medicine.disease, Nutritional Diseases, Diet, Mice, Inbred C57BL, Endocrinology, Diabetes Mellitus, Type 2, Immune System, biology.protein, Inbred C57BL"*"Mice, lcsh:Q, Insulin Resistance
Abstract: International audience; Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFalpha expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
Published: 2014
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36. Oral administration of cholera toxin B-insulin conjugates protects NOD mice from autoimmune diabetes by inducing CD4+ regulatory T-cells

Author: Cecil Czerkinsky, Charles Thivolet, Jan Holmgren, Corinne Ploix, Annie Durand, and I. Bergerot
Subjects: CD4-Positive T-Lymphocytes, Male, Cholera Toxin, medicine.medical_specialty, Transcription, Genetic, Endocrinology, Diabetes and Metabolism, medicine.disease_cause, Immune tolerance, Interferon-gamma, Mice, Immune system, Antigen, Mice, Inbred NOD, Internal medicine, Internal Medicine, medicine, Animals, Humans, Insulin, Mesenteric lymph nodes, NOD mice, Mice, Inbred BALB C, Mice, Inbred C3H, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Cholera toxin, Peripheral tolerance, Recombinant Proteins, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Endocrinology, Lymphocyte Transfusion, Immunology, Cytokines, Female, Lymph Nodes, Lymph, business, Spleen
Abstract: Restoration of peripheral tolerance to target autoantigens during autoimmune diseases has met with several limitations because of the limited efficacy of this approach in an already immune host. To optimize the induction of tolerance, we have shown that feeding insulin conjugated to cholera toxin B-subunit (CTB), a potent mucosal adjuvant, reduced by 5,000 the amounts of antigen necessary for delaying diabetes onset in NOD mice. To analyze these protective mechanisms, we have performed cotransfer experiments using splenocytes from young females fed once with 10 microg of CTB-insulin, mixed with diabetogenic T-cells, and intravenously injected into irradiated syngeneic male recipients. We demonstrated that the delayed onset of diabetes relied on CD4+ T-cells. We studied the cytokine production from plate-bound anti-CD3-stimulated cells. Higher interleukin (IL)-4 amounts were observed in both splenocytes and pancreatic lymph node (PLN) cell cultures from CTB-insulin-fed mice as soon as 4 h after the feeding. An increase in the levels of transforming growth factor-beta was seen after 24 h only in the mesenteric lymph nodes (MLN). In both of these organs, a reduction of gamma-interferon (IFN-gamma) production occurred after CTB-insulin treatment, at 24 h in the PLN and at 7 days in the MLN. Reverse transcription-polymerase chain reaction analysis indicated an increase in the level of IL-4 and a reduction in IFN-gamma transcripts in the PLN of mice treated orally with CTB-insulin and of the recipients of regulatory T-cells. Using different strains of congenic NOD mice at the Thy1 locus, we showed that protection was associated with the accumulation of T-cells from CTB-insulin-fed mice in the lymph nodes from draining sites containing functional islets, i.e., the PLN in normal mice and the renal lymph nodes after a syngeneic islet graft under the kidney capsule of streptozotocin-treated mice. Taken together, our results clearly indicate that oral administration of CTB-insulin conjugates in NOD mice produced a shift from a T-helper type 1 to a type 2 profile with the induction of antigen-specific regulatory CD4+ T-cells in the vicinity of the mucosal barrier and close to the inflamed islets.
Published: 1999
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37. Endoplasmic reticulum stress contributes to heart protection induced by cyclophilin D inhibition

Author: Lionel Augeul, Michel Ovize, Johanna Decorps, Annie Durand, and Elise Belaidi
Subjects: Male, medicine.medical_specialty, Physiology, Glucose-regulated protein, Myocardial Infarction, NIM811, Cyclosporins, Myocardial Reperfusion Injury, Taurochenodeoxycholic Acid, Cyclophilins, Mice, chemistry.chemical_compound, Physiology (medical), Internal medicine, medicine, Animals, Inner mitochondrial membrane, Endoplasmic Reticulum Chaperone BiP, Mice, Knockout, Cardioprotection, biology, Endoplasmic reticulum, Heart, Endoplasmic Reticulum Stress, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Biochemistry, chemistry, Mitochondrial permeability transition pore, Mitochondrial Membranes, Cyclosporine, biology.protein, Unfolded protein response, Cardiology and Cardiovascular Medicine, Reperfusion injury, Cyclophilin D
Abstract: Preventing cyclophilin D (cypD) translocation to the inner mitochondrial membrane can limit lethal reperfusion injury through the inhibition of the opening of the mitochondrial permeability transition pore. Inhibition or loss of function of cypD may also result into an endoplasmic reticulum (ER) stress that has been shown to alter cell survival. We therefore questioned whether ER stress might play a role in the protection induced by CypD deficiency or inhibition. CypD-KO and NIM811 (a CypD inhibitor)-treated mice were subjected to a prolonged ischemia–reperfusion (I/R). Area at risk and infarct size was measured using blue dye and triphenyltetrazolium chloride staining. ER stress markers were measured in the hearts during the reperfusion phase. As expected, cypD-KO mice exhibited a decreased infarct size when compared to wild-type mice (8 ± 1 vs. 20 ± 4 % of left ventricular weight; p
Published: 2013
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38. Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice

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

Author: Charlotte Ménage, Annie Durand, Mbaye Diop, and Marie-Noëlle Guerrault
Subjects: Pharmacology (medical)
Abstract: Introduction Au meme titre que les medicaments per os ou injectables, l’erreur d’administration de gaz a usage medical fait partie des « Never Events » proposes par le National Health Service en Angleterre. Les gaz medicaux sont aussi concernes par la certification V2014. Ceci en fait un axe prioritaire d’amelioration de la prise en charge medicamenteuse. L’objectif de cette etude est d’evaluer l’etat des connaissances sur les gaz medicaux puis de proposer et mettre en place des mesures correctives. Materiels et methode Le questionnaire et sa grille d’evaluation ont ete etablis par un interne et deux pharmaciens a partir de la litterature et de supports de formation. Anonyme et individuel, il comporte 16 questions au choix multiple, reparties equitablement en 8 axes correspondant aux etapes du circuit des gaz medicaux : statut et proprietes des gaz (A), conditionnement (B), prescription et dispensation (C), manutention et stockage (D), utilisation des bouteilles (E), utilisation des prises (F), controle et secours (G), les differents gaz medicaux (H). Chaque axe est evalue sur 8 points. La mediane ainsi que les minimum et maximum ont ete calcules par axe et par profession. Un axe est considere acquis si la mediane est superieure a 6 points, non acquis si elle est inferieure a 4 points, ou partiellement acquis entre 4 et 6. Trois cent cinquante questionnaires ont ete distribues dans les services de l’hopital. Les medecins, sage-femmes, infirmiers, pharmaciens, preparateurs, internes, externes et etudiants ont ete invites a y repondre en indiquant leur profession. Apres un delai de 15 jours, les questionnaires retournes a la pharmacie ont ete analyses. Resultats et discussion Les 94 questionnaires recuperes ont ete analyses. Pour les medecins ( n = 19), les axes C, D, H sont acquis tandis que pour les internes en medecine ( n = 3), les axes A, D, F, H le sont. Les axes A, C, D, E sont acquis par les pharmaciens ( n = 9), ce qui n’est pas le cas des internes en pharmacie ( n = 4) pour qui seuls les axes C et E le sont. Les infirmiers ( n = 49) et preparateurs ( n = 9) ont acquis l’axe D mais pas l’axe B. De plus les preparateurs n’ont pas acquis les axes E, F, H. L’etudiant infirmier ( n = 1) a acquis les axes C et D mais B, E, F restent non acquis. Les axes non mentionnes sont partiellement acquis. Quatre mesures correctives ont ete proposees et mises en place. Tout d’abord, les reponses et resultats au questionnaire ont ete transmis aux participants. Un guide sur les gaz medicaux, visuel et pedagogique, a ensuite ete cree. Il reprend les differentes etapes du circuit des gaz medicaux en insistant sur les risques associes et detaille les differents gaz disponibles sur l’hopital. La priorite sera donnee au conditionnement, a l’utilisation des bouteilles et des prises. Sur cette base, une formation pour l’ensemble du personnel va etre menee. Elle a deja ete realisee a la pharmacie. Enfin, la participation a la formation sur les armoires de secours, deja organisee plusieurs fois par an, a ete encouragee. Conclusion Le questionnaire a permis la sensibilisation du personnel a la problematique des gaz medicaux et d’amorcer la securisation du circuit.
Published: 2014
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40. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice

Author: Annie Durand, Jennifer Rieusset, Simone Peyrol, Marie-Agnès Chauvin, Hubert Vidal, C. Bonnard, Béatrice Morio, Emilie Chanseaume, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), IFR Laennec (IL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, This work was supported by grants of INSERM, the French National Research Agency (ANR-05-PCOD-012) and the French National Program on Diabetes Research (to J.R), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vericel, Evelyne, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Sucrose, Mitochondrial Diseases, Muscle Fibers, Skeletal, Type 2 diabetes, medicine.disease_cause, Mice, 0302 clinical medicine, Myocyte, MESH: Animals, 2. Zero hunger, 0303 health sciences, MESH: Muscle, Skeletal, MESH: Muscle Fibers, Skeletal, MESH: Oxidative Stress, MESH: Mitochondria, Muscle, MESH: Reactive Oxygen Species, MESH: Mitochondrial Diseases, General Medicine, 3. Good health, MESH: Insulin Resistance, medicine.anatomical_structure, MESH: Dietary Fats, Research Article, MESH: Diabetes Mellitus, Type 2, Muscle tissue, medicine.medical_specialty, Biology, 03 medical and health sciences, Insulin resistance, MESH: Diet, MESH: Mice, Inbred C57BL, Internal medicine, Diabetes mellitus, medicine, Animals, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, MESH: Sucrose, Skeletal muscle, medicine.disease, Dietary Fats, MESH: Male, Diet, Mitochondria, Muscle, Mice, Inbred C57BL, Oxidative Stress, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, Diabetes Mellitus, Type 2, Mitochondrial biogenesis, Insulin Resistance, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Oxidative stress
Abstract: International audience; Mitochondrial dysfunction in skeletal muscle has been implicated in the development of type 2 diabetes. However, whether these changes are a cause or a consequence of insulin resistance is not clear. We investigated the structure and function of muscle mitochondria during the development of insulin resistance and progression to diabetes in mice fed a high-fat, high-sucrose diet. Although 1 month of high-fat, high-sucrose diet feeding was sufficient to induce glucose intolerance, mice showed no evidence of mitochondrial dysfunction at this stage. However, an extended diet intervention induced a diabetic state in which we observed altered mitochondrial biogenesis, structure, and function in muscle tissue. We assessed the role of oxidative stress in the development of these mitochondrial abnormalities and found that diet-induced diabetic mice had an increase in ROS production in skeletal muscle. In addition, ROS production was associated with mitochondrial alterations in the muscle of hyperglycemic streptozotocin-treated mice, and normalization of glycemia or antioxidant treatment decreased muscle ROS production and restored mitochondrial integrity. Glucose- or lipid-induced ROS production resulted in mitochondrial alterations in muscle cells in vitro, and these effects were blocked by antioxidant treatment. These data suggest that mitochondrial alterations do not precede the onset of insulin resistance and result from increased ROS production in muscle in diet-induced diabetic mice.
Published: 2008
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41. Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice

Author: Annie Durand, C. Bonnard, Hubert Vidal, and Jennifer Rieusset
Subjects: Male, medicine.medical_specialty, Hypoxanthine Phosphoribosyltransferase, Sucrose, Endocrinology, Diabetes and Metabolism, Adipokine, Adipose tissue, Biology, Polymerase Chain Reaction, Diabetes Mellitus, Experimental, Mice, Endocrinology, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Dietary Carbohydrates, Animals, Receptor, Adiponectin receptor 1, Adiponectin, Adenylate Kinase, AMPK, Skeletal muscle, General Medicine, medicine.disease, Animal Feed, Dietary Fats, Mice, Inbred C57BL, medicine.anatomical_structure, Receptors, Adiponectin
Abstract: Aim A high-fat and high-sucrose diet (HFHSD) is usually used to induce type 2-like diabetes in animal models. We investigated the effect of HFHSD on serum and tissue levels of adiponectin, its receptors and AMP-activated protein kinase (AMPK) activity in adipose tissue, skeletal muscle and the liver. Methods C57Bl/6 male mice were fed either a standard diet or an HFHSD for four and 16 weeks, during which time glucose and insulin tolerance tests were performed. Results After four weeks, the HFHSD-fed mice were obese and glucose-intolerant and, after 16 weeks, they were obese and diabetic. In general, four weeks of HFHSD feeding did not modify either circulating or tissue adiponectin levels, nor adiponectin receptors or AMPK activity in the tissues studied. A significant increase of circulating adiponectin was observed after 16 weeks of HFHSD feeding, whereas adiponectin expression was decreased in adipose tissue. Muscle expression of adiponectin was increased at 16 weeks in terms of both mRNA and protein levels, and correlated to adipose-specific gene expression. However, AdipoR1 mRNA levels and AMPK activity were decreased in muscle at 16 weeks, suggesting decreased sensitivity to adiponectin in the muscle of diabetic mice. Finally, liver adiponectin expression was detectable only at protein levels and was increased in HFHSD mice at 16 weeks, suggesting "contamination" by circulating adiponectin. AdipoR2 mRNA levels were significantly decreased, whereas AMPK was increased, in the liver at 16 weeks. Conclusion Overall, our data suggest that HFHSD-induced diabetes is not associated with adiponectin deficiency, but with tissue-specific defects of adiponectin-receptor expression and AMPK activity.
Published: 2007

42. Lack of association of IL-10 promoter gene variants with type 1 diabetes in a French population

Author: Frédéric Reynier, Charles Thivolet, Audrey Rosa, Annie Durand, Umar Jhumka, Bruno Mougin, Nathalie Bendelac, Annick Lecoq, Malick Paye, Marc Nicolino, Pierre Miossec, and Marie-Angélique Cazalis
Subjects: Adult, Male, Adolescent, Immunology, Population, Human leukocyte antigen, Biology, White People, Gene Frequency, Polymorphism (computer science), medicine, Genetic predisposition, Immunology and Allergy, Humans, Genetic Predisposition to Disease, Allele, education, Child, Promoter Regions, Genetic, Gene, Autoantibodies, Genetics, education.field_of_study, Type 1 diabetes, Molecular Epidemiology, Polymorphism, Genetic, Glutamate Decarboxylase, Infant, General Medicine, medicine.disease, Interleukin-10, Diabetes Mellitus, Type 1, Child, Preschool, Female, France, TCF7L2
Abstract: Although genetic predisposition to type 1 diabetes shows a strong association with human leukocyte antigen (HLA) class II alleles, additional genes may influence the immune process and the progression of beta cell loss. Preliminary reports suggested that IL-10 gene polymorphisms contribute to susceptibility to type 1 diabetes. We analyzed the frequencies of three main variants of the promoter region of the IL-10 gene at the positions -1082, -819, and -592 in a cohort of 358 type 1 diabetic patients representing the same regional population pattern and 519 controls from the same region using an enzyme-linked oligonucleotide sorbent assay. We did not find any statistical association in the entire cohort or after stratification for high-risk HLA-DQ alleles. However, the IL-10 -1082 polymorphism was significantly associated with GAD and IA-2 antibodies at clinical onset. Such polymorphism is known to be associated with the reduction of secreted IL-10 which may support the concept of accelerated Th-1 T-cell reactivity. In conclusion, IL-10 promoter gene variants may contribute, but to a minor extent, to disease susceptibility in juvenile type 1 diabetes and should not be included in the routine genetic screening of high-risk individuals.
Published: 2005

43. O57 L’induction d’un stress du réticulum endoplasmique par le palmitate n’est pas impliquée dans le développement de l’insulino-résistance musculaire

Author: Hubert Vidal, Jennifer Rieusset, Annie Durand, Marie-Caroline Michalski, and Marie-Agnès Chauvin
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Introduction Une augmentation des acides gras libres plasmatiques est associee a l'obesite et au diabete de type 2, et participe au developpement de l'insulino-resistance. Plus particulierement, les acides gras satures (ex : le palmitate) sont connus pour avoir des effets deleteres via l'induction d'un stress du reticulum endoplasmique (RE) dans de nombreux types cellulaires. Neanmoins, on ne sait pas a l'heure actuelle si les effets du palmitate sur la sensibilite a l'insuline impliquent un stress du RE dans le muscle squelettique. Materiels et methodes Nous avons etudie les repercussions d'un traitement au palmitate sur l'homeostasie du RE et sur la sensibilite a l'insuline, a la fois in vitro , dans des C2C12, et in vivo , dans le muscle de souris soumises a une diete enrichie en huile de palme (souris HPD). L'implication du stress du RE dans l'insulino-resistance induite par le palmitate a ete determinee en traitant des myotubes soit avec du TUDCA (tauroursodeoxycholic acid) soit en surexprimant la chaperone Grp78 dans les C2C12. Resultats Nous demontrons que le palmitate (200–700 μM, 3–48 heures) induit un stress du RE et altere la signalisation de l'insuline (inhibition de la phosphorylation d'Akt induite par l'insuline) dans les myotubes differencies. L'inhibition du stress du RE, soit par un traitement au TUDCA soit par la surexpression de la proteine chaperone Grp78, n'ameliore pas l'insulino-resistance induite par le palmitate. L'induction d'un stress du RE par le palmitate est confirmee in vivo dans le muscle gastrocnemius de souris HPD, alors que la sensibilite a l'insuline du muscle n'est pas encore alteree apres 8 semaines de traitement. Conclusion L'ensemble de ces donnees demontrent que l'induction du stress du RE par le palmitate n'est pas impliquee dans le developpement de l'insulino-resistance musculaire.
Published: 2011
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44. O14 Une altération des transferts calcique du RE vers la mitochondrie chez la souris invalidée pour la cyclophiline D induit un stress du RE et une insulino-résistance hépatique

Author: Jennifer Rieusset, Amélie Bravard, Jérémy Fauconnier, B. Bartosh, Michel Ovize, Annie Durand, E. Blond, Hubert Vidal, Guillaume Vial, Marie Demion, Geoffrey Teixeira, Alain Lacampagne, Ludovic Gomez, Marie-Agnès Chauvin, Pierre Theurey, M. Paillard, Fabien Zoulim, Emily Tubbs, Elise Belaidi, and Maud Michelet
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Introduction S’il est bien admis que l’insulino-resistance hepatique (IRH) est associee a des alterations mitochondriales, un stress du reticulum endoplasmique (RE) et une perturbation de l’homeostasie calcique, on ne sait pas a l’heure actuelle si ces defauts representent des facteurs independants. Nous avons teste l’hypothese qu’ils sont inter-relies, via une alteration des echanges calciques au niveaux des points de contact entre les deux oragnites, appeles mitochondria-associated membranes (MAM). Materiels et methodes Sur la base de donnees recentes impliquant une chaperone mitochondriale, la cyclophiline D, dans la regulation de l’homeostasie calcique, du RE et du metabolisme glucidique, nous avons utilise des souris invalidees pour la cypD (cypD-KO) et des approches pharmacologiques et geniques in vitro pour etudier le role de la signalisation calcique mediee par IP3R au niveau des MAM dans l’IRH. Resultats Les souris cypD-KO presentent un stress du RE hepatique responsable d’une steatose, d’une IRH et d’une perturbation de l’homeostasie glucidique, puisque ces alterations sont prevenues par une inhibition du stress du RE (traitement au TUDCA ou surexpression hepatique de la chaperone Grp78). Ce stress du RE est lie a un defaut d’interaction et d’echange calcique entre le RE et la mitochondrie dans les hepatocytes de souris cypD-KO. L’ensemble de ces donnees sont reproduites in vitro dans des cellules HuH7 ou la cypD a ete inhibee soit par des traitements pharmacologiques (cyclosporine et NIM811) soit par un ARNi specifique. Enfin, nous demontrons que les alterations de la signalisation de l’insuline induite par la perte de cypD sont mediees par une activation de la PKCɛepsi; plutot que de la JNK. Conclusion Nos resultats demontrent un nouveau role de la cypD dans les interactions structurales et fonctionnelles entre le RE et la mitochondrie et un role cle de la signalisation calcique mediee par IP3R au niveau des MAM dans l’insulino-resistance hepatique.
Published: 2013
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45. P160 Implication du stress oxydant dans la dysfonction des cellules beta induite par les glucocorticoïdes et PGC-1a

Author: Bérengère Valtat, Annie Durand, Mathieu Armanet, E. Ramond, Jennifer Rieusset, Jean-Pierre Riveline, Bernadette Breant, and B. Blondeau
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Rationnel Notre equipe s’interesse aux regulateurs de la fonction beta pancreatique. Nos travaux precedents ont montre que la voie des glucocorticoides (GC) inhibe le developpement et la fonction des cellules beta. Plus specifiquement, nous avons montre que la surexpression de PGC-1a, co-regulateur du recepteur des GC, specifiquement dans les cellules beta (souris Ins-PGC-1a) entraine une reduction de la secretion d’insuline, de la masse de cellules beta et de l’expression de Pdx1, facteur de transcription-cle des cellules beta. Or PGC-1a controle la biogenese mitochondriale et la production d’especes reactives de l’oxygene (ERO). Notre objectif est donc de definir si la surexpression de PGC-1a dans les cellules beta induit un stress oxydant qui pourrait participer au phenotype des souris. Materiels et methodes La surexpression de PGC-1a a ete etudiee chez nos souris Ins-PGC1a et dans une lignee de cellules beta de souris (Min6) traitees aux GC ou transduites par un adenovirus surexprimant PGC-1a. Nous avons mesure l’expression de Pdx1, de marqueurs du stress oxydant (SOD1, SOD2 et catalase), quantifie les especes reactives de l’oxygene (ERO) et estime la quantite de mitochondrie par cellule par quantification de l’ADN mitochondrial. Resultats Nous avons montre dans les ilots des souris InsPGC-1a une augmentation de l’expression des marqueurs du stress oxydant et de la quantite d’ERO. La surexpression moderee (par traitement aux GC) ou massive (par un adenovirus) de PGC-1a dans les cellules Min6 entraine une augmentation de l’expression des genes marqueurs du stress oxydant, partiellement reversible par l’anti-oxydant N-acetyl-cysteine. La surexpression massive de PGC-1a par adenovirus augmente la quantite de mitochondries et des ERO. En revanche, le stress oxydant n’est pas responsable de la diminution de Pdx1 induite par PGC-1a ou les GC. Conclusion Nos resultats suggerent que la dysfonction des cellules beta induite par les GC provient d’un stress oxydant suite a l’activation d’une biogenese mitochondriale induite par PGC-1a.
Published: 2012
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46. O36 Étude des mécanismes de l’inflammation du muscle squelettique en relation avec l’insulino-résistance

Author: Annie Durand, David Patsouris, Marie-Caroline Michalski, Hubert Vidal, J.J. Cao, Jennifer Rieusset, and Marie-Agnès Chauvin
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Introduction Le diabete type 2 (DT2) est associe a une inflammation a bas bruit et une accumulation de macrophages pro-inflammatoires principalement dans le tissu adipeux. Cette inflammation participerait au developpement de l’insulino-resistance (IR), puisque les cytokines pro-inflammatoires inhibent la signalisation de l’insuline. Le muscle squelettique est le principal tissu utilisateur de glucose en reponse a l’insuline, et une cible privilegiee des alterations en situation d’IR. Neanmoins, il existe tres peu d’informations sur le statut inflammatoire du muscle dans le cadre du DT2. L’objectif de notre etude a ete d’etudier l’infiltration de macrophages dans le muscle squelettique de differents modeles de souris diabetiques et le role des lipides dans l’attraction des macrophages. Materiels et methodes Nous avons mesure l’infiltration de macrophages (immunohistochimie) et l’expression de cytokines pro- et anti-inflammatoires (PCR en temps reel) dans le muscle gastrocnemius de souris ob/ob et de souris soumises soit a une diete riche en lipides (HFD 45 %) soit a des dietes enrichies en differents types d’acide gras (tournesol, colza, beurre ou palme, 20 %). L’effet benefique d’un traitement antidiabetique (Rosiglitazone) a egalement ete etudie chez les souris HFD. L’implication des lipides dans l’attraction des macrophages a ete etudie in vitro en exposant des macrophages Raw264.7 a des milieux conditionnes (MC) de C2C12 incubes ou pas en presence de palmitate (700 μm). Resultats Nous observons une infiltration de macrophages dans le muscle gastrocnemius des differents modeles de souris diabetiques, qui est positivement correlee a l’expression des cytokines pro-inflammatoires (TNFa, IL1b) et a IR. Le recrutement des macrophages semble faire intervenir la secretion de chemokines (MCP1) par les cellules musculaires, puisque l’exposition des Raw264.7 a des MC de C2C12 exposes au palmitate augmente leur migration (p Conclusion Nos resultats demontrent que le DT2 s’accompagne d’une infiltration de macrophages pro-inflammatoires dans le muscle squelettique, qui pourrait participer a l’installation de l’IR.
Published: 2012
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47. Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals

Author: A. Stefanutti, Pierre Chatelain, Werner A. Scherbaum, M. Tappaz, J. Orgiazzi, J. Petersen, Annie Durand, Charles Thivolet, and B. Vialettes
Subjects: Proband, Adult, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Glutamate decarboxylase, Immunoenzyme Techniques, Islets of Langerhans, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Family, Child, Autoantibodies, Autoimmune disease, Type 1 diabetes, geography, geography.geographical_feature_category, biology, Glutamate Decarboxylase, Autoantibody, HLA-DR Antigens, medicine.disease, Islet, Prognosis, Molecular Weight, Endocrinology, Diabetes Mellitus, Type 1, Immunology, biology.protein, Antibody
Abstract: The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic autoantibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell autoantibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2=182, p=0.0001). None of the relatives with low genetic risk (n=64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling. Altogether, the simultaneous presence of autoantibodies to glutamate decarboxylase and high titre islet cell autoantibody increases the positive predictive value for the disease from 66% to 75%. This study indicates therefore that autoantibodies to glutamate decarboxylase detected by an immunotrapping enzyme activity assay are additional predictive markers for future development of Type 1 diabetes and should be now prospectively studied in high risk individuals as well as other autoantibodies to Beta-cell autoantigens.
Published: 1992

48. P250 Implication de la xanthine oxydase dans la production de ROS musculaire induite par l’hyperglycémie

Author: Amélie Bravard, Hubert Vidal, Roland Favier, Jennifer Rieusset, C. Bonnard, and Annie Durand
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Introduction Le stress oxydant associe a l’hyperglycemie est une caracteristique classique du diabete. L’augmentation de la production de radicaux libres (RL) fait intervenir differentes voies intracellulaires, mais les sources precises des RL sont encore mal definies dans les tissus sensibles a l’insuline, comme le muscle squelettique. Le but de notre etude etait donc de caracteriser les sites intracellulaires de production des RL induite par l’hyperglycemie dans le muscle squelettique de souris rendues diabetiques par un traitement a la streptozotocine (STZ). Les effets d’un traitement a l’insuline ou par des antioxydants ont egalement ete etudies. Resultats Les souris traitees a la STZ presentent une forte hyperglycemie associee a un stress oxydant circulant et musculaire. L’augmentation du stress oxydant est liee a une induction de la production de RL au niveau des mitochondries et de la xanthine oxydase (XO). De facon interessante, un traitement a l’insuline diminue l’hyperglycemie et ameliore le stress oxydant circulant et musculaire. Ces effets sont associes a une diminution de la production de RL induite a la fois par les mitochondries et la XO. De plus, la production de RL associee a des concentrations elevees de glucose est inhibee in vitro par la rotenone et l’oxypurinol dans des cellules musculaires, confirmant l’implication du complexe I des mitochondries et de la XO. Enfin, un traitement des souris STZ a l’oxypurinol diminue le stress oxydant systemique et musculaire, validant in vivo l’implication de la XO dans la production de RL associee a l’hyperglycemie. Conclusion L’ensemble de ces travaux demontrent l’implication du complexe I des mitochondries et de la XO dans la production de RL associee a l’hyperglycemie, mettant ainsi en evidence de nouvelles cibles responsables des dommages musculaires associes a l’hyperglycemie.
Published: 2009
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49. Insulin prevents adoptive cell transfer of diabetes in the autoimmune non-obese diabetic mouse

Author: Annie Durand, M. Bonnard, C. Thivolet, J. Orgiazzi, Pierre Bedossa, and E. Goillot
Subjects: Male, medicine.medical_specialty, Adoptive cell transfer, Necrosis, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin Antibodies, T-Lymphocytes, Immunotherapy, Adoptive, Autoimmune Diseases, Diabetes Mellitus, Experimental, Islets of Langerhans, Mice, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Splenocyte, Animals, Insulin, geography, geography.geographical_feature_category, business.industry, medicine.disease, Islet, Mice, Mutant Strains, Endocrinology, Female, medicine.symptom, Beta cell, business, Insulitis
Abstract: Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p
Published: 1991

50. P10 Les altérations mitochondriales résultent d’un stress oxydant dans le muscle squelettique de souris diabétiques

Author: C. Bonnard, Hubert Vidal, Annie Durand, Béatrice Morio, Jennifer Rieusset, Emilie Chanseaume, S. Peyrol, and Marie-Agnès Chauvin
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Introduction Des dysfonctionnements mitochondriaux dans le muscle squelettique seraient impliques dans le developpement du diabete de type 2. Cependant, si ces alterations sont une cause ou une consequence de l’insulino-resistance n’est toujours pas determine. Materiels et methodes Nous avons donc etudie la structure et les fonctions mitochondriales au cours du developpement de l’insulino-resistance, induite chez l’animal par une diete riche en lipides et en sucrose. Resultats Aucune alteration mitochondriale n’est mis en evidence dans le muscle de souris prediabetiques, alors que la biogenese, la structure et les fonctions mitochondriales sont alterees dans le muscle de souris diabetiques. D’autre part, nous demontrons que le stress oxydant musculaire est un element causal majeur dans ces alterations mitochondriales puisque 1. il existe une augmentation de la production locale de radicaux libres (RL) uniquement dans le muscle squelettique de souris diabetiques, associee a une hyperglycemie et hyperlipidemie, 2. Une production de RL est egalement associee a des alterations mitochondriales dans le muscle de souris de souris rendues hyperglycemiques par un traitement a la streptozotocine, 3. Chez ces souris, la normalisation de la glycemie par un traitement a l’insuline ou a la phlorizine, ainsi qu’un traitement antioxydant, diminuent la production de RL et restaurent les alterations mitochondriales, et 4. l’induction d’une production de RL par du glucose ou des lipides, in vitro, altere la densite et les fonctions mitochondriales dans des cellules musculaires en culture, et ces effets sont restaures par un traitement antioxydant. Conclusion L’ensemble de ces donnees suggerent que les alterations mitochondriales ne sont pas causales dans le developpement de l’insulino-resistance, mais plutot la consequence d’un stress oxydant musculaires associe a l’hyperglycemie et l’hyperlipidemie des souris diabetiques.
Published: 2008
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