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1. Combinatorial, additive and dose-dependent drug-microbiome associations

Author

Forslund, SK, Chakaroun, R, Zimmermann-Kogadeeva, M, Markó, L, Aron-Wisnewsky, J, Nielsen, T, Moitinho-Silva, L, Schmidt, TSB, Falony, G, Vieira-Silva, S, Adriouch, S, Alves, RJ, Assmann, K, Bastard, J-P, Birkner, T, Caesar, R, Chilloux, J, Coelho, LP, Fezeu, L, Galleron, N, Helft, G, Isnard, R, Ji, B, Kuhn, M, Le Chatelier, E, Myridakis, A, Olsson, L, Pons, N, Prifti, E, Quinquis, B, Roume, H, Salem, J-E, Sokolovska, N, Tremaroli, V, Valles-Colomer, M, Lewinter, C, Søndertoft, NB, Pedersen, HK, Hansen, TH, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Batisse, J-P, Belda, E, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Collet, J-P, Dao, M-C, Djebbar, M, Doré, A, Engelbrechtsen, L, Fellahi, S, Fromentin, S, Galan, P, Gauguier, D, Giral, P, Hartemann, A, Hartmann, B, Holst, JJ, Hornbak, M, Hoyles, L, Hulot, J-S, Jaqueminet, S, Jørgensen, NR, Julienne, H, Justesen, J, Kammer, J, Krarup, N, Kerneis, M, Khemis, J, Kozlowski, R, Lejard, V, Levenez, F, Lucas-Martini, L, Massey, R, Martinez-Gili, L, Maziers, N, Medina-Stamminger, J, Montalescot, G, Moute, S, Neves, AL, Olanipekun, M, Le Pavin, LP, Poitou, C, Pousset, F, Pouzoulet, L, Rodriguez-Martinez, A, Rouault, C, Silvain, J, Svendstrup, M, Swartz, T, Vanduyvenboden, T, Vatier, C, Walther, S, Gøtze, JP, Køber, L, Vestergaard, H, Hansen, T, Zucker, J-D, Hercberg, S, Oppert, J-M, Letunic, I, Nielsen, J, Bäckhed, F, Ehrlich, SD, Dumas, M-E, Raes, J, Pedersen, O, Clément, K, Stumvoll, M, Bork, P, The MetaCardis Consortium (Hoyles, L.), European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (UCPH), University of New South Wales [Sydney] (UNSW), Paul Scherrer Institute (PSI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Heidelberg University, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Gothenburg (GU), Imperial College London, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chalmers University of Technology [Gothenburg, Sweden], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Biobyte Solutions [Heidelberg, Germany] (BS), IT University of Copenhagen (ITU), Sahlgrenska University Hospital [Gothenburg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, McGill University and Genome Quebec Innovation Centre, Helmholtz Institute Ulm (HIU), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Würzburg = Universität Würzburg, Yonsei University, MetaCardis Consortium*: Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin, Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann, Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles, Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura Martinez-Gili, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault, Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Dumas, Marc-Emmanuel, Universität Leipzig [Leipzig], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Henri Mondor, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-1901(ex CIC-1421)), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK

Subjects
Clostridiales, Science & Technology, Multidisciplinary, ANTIBIOTIC USE, IMPACT, Microbiota, [SDV]Life Sciences [q-bio], HUMAN GUT MICROBIOME, Atherosclerosis, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, PROTON PUMP INHIBITORS, Cardiovascular and Metabolic Diseases, GUIDELINE, Metabolome, MANAGEMENT, Humans, Science & Technology - Other Topics, ALTERS
Abstract

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. ispartof: NATURE vol:600 issue:7889 pages:500-+ ispartof: location:England status: published

Published
2021

2. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials

Author

Argente J, Gonneau-Lejeune J, Wabitsch M, Poitou C, Connors H, Swain J, Stewart M, Kohlsdorf K, Chung Wk, Lia Puder, Yuan G, Clement K, van den Akker E, Farooqi Is, Peter Kühnen, Gordon G, De Waele K, and Bahm A

Subjects
Agonist, Setmelanotide, medicine.medical_specialty, Endocrinology, business.industry, POMC Deficiency, medicine.drug_class, Internal medicine, medicine, Open label, Severe obesity, business
Published
2021

3. Effectiveness of exercise training after bariatric surgery-a systematic literature review and meta-analysis

Author

Bellicha, Alice, Ciangura, C, Poitou, C, Portero, P, Oppert, J-M, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-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)-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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), and Bellicha, Alice

Subjects
Bariatric surgery, obesity, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, physical activity, exercise training, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; We aimed to conduct a systematic review and meta-analysis of controlled trials assessing exercise training programs in patients with obesity undergoing bariatric surgery. We systematically searched exercise training studies performed after bariatric surgery published up to June 2017. Studies reporting changes in body composition, physical fitness, functional capacity, objectively measured physical activity, quality of life or relevant health outcomes were included. The review protocol is available from PROSPERO (CRD42017069380). Meta-analyses were conducted using random-effects models when data were available from at least five articles. Twenty articles were included, describing 16 exercise training programs, of which 15 were included in the meta-analysis. Overall, exercise training was associated with higher weight loss (mean difference: À2.4 kg, 95% CI: À4.2; À0.6, I 2 = 49%, n = 12), higher fat mass loss (À2.7 kg, 95% CI: À4.5; À1.0, I 2 = 50%, n = 8) and improved VO 2 max and functional walking (standardized mean difference: 0.86, 95% CI: 0.29; 1.44, I 2 = 57%, n = 6; 1.45, 95% CI: 0.32; 2.58, I 2 = 89%, n = 6, respectively). Exercise training was not associated with lean body mass changes. In conclusion, exercise training programs performed after bariatric surgery were found effective to optimize weight loss and fat mass loss and to improve physical fitness, although no additional effect on lean body mass loss was found.

Published
2018

4. The advanced-DiaRem score improves prediction of diabetes remission 1 year post-Roux-en-Y gastric bypass

Author

Aron-Wisnewsky, J., Sokolovska, N., Liu, Y. J., Comaneshter, D. S., Vinker, S., Pecht, T., Poitou, C., Oppert, J. M., Bouillot, J. L., Genser, L., Dicker, D., Zucker, Jean-Daniel, Rudich, A., and Clement, K.

Subjects
Bariatric surgery, Type 2 diabetesmellitus, Diabetes remission, Obese
Abstract

Aims/hypothesis Not all people with type 2 diabetes who undergo bariatric surgery achieve diabetes remission. Thus it is critical to develop methods for predicting outcomes that are applicable for clinical practice. The DiaRem score is relevant for predicting diabetes remission post-Roux-en-Y gastric bypass (RYGB), but it is not accurate for all individuals across the entire spectrum of scores. We aimed to develop an improved scoring system for predicting diabetes remission following RYGB (the Advanced-DiaRem [Ad-DiaRem]). Methods We used a retrospective French cohort (n = 1866) that included 352 individuals with type 2 diabetes followed for 1 year post-RYGB. We developed the Ad-DiaRemin a test cohort (n = 213) and examined its accuracy in independent cohorts from France (n = 134) and Israel (n = 99). Results Adding two clinical variables (diabetes duration and number of glucose-lowering agents) to the original DiaRem and modifying the penalties for each category led to improved predictive performance for Ad-DiaRem. Ad-DiaRem displayed improved area under the receiver operating characteristic curve and predictive accuracy compared with DiaRem (0.911 vs 0.856 and 0.841 vs 0.789, respectively; p = 0.03); thus correcting classification for 8% of those initially misclassified with DiaRem. With Ad-DiaRem, there were also fewer misclassifications of individuals with mid-range scores. This improved predictive performance was confirmed in independent cohorts. Conclusions/interpretation We propose the Ad-DiaRem, which includes two additional clinical variables, as an optimised tool with improved accuracy to predict diabetes remission 1 year post-RYGB. This tool might be helpful for personalised management of individuals with diabetes when considering bariatric surgery in routine care, ultimately contributing to precision medicine.

Published
2017

6. Impairment of intestinal barrier integrity in human obesity: involvement of dietary lipids and links with bioclinical phenotypes

Author

Genser, L., Soula, H., Dong, L., Trystram, L. Barbot, Salem, J. -E, Vaillant, J. -C, Oppert, J. -M, Laugerette, F., Michalski, M. -C, Rousset, M., Brot-Laroche, E., Leturque, A., Clement, K., Sophie Thenet, Poitou, C., ProdInra, Migration, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition - Institute of Cardiometabolism and Nutrition, 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), ICAN, AP-HP, Benjamin Delessert Institute, and GLN

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

8. Noninvasive diagnosis of nonalcoholic steatohepatitis disease based on clinical decision support system

Author

Douali, N., Abdennour, M., Sasso, M., Miette, V., Tordjman, J., Bedossa, P., Veyrie, N., Poitou, C., Aron-Wisnewsky, J., Clément, K., Jaulent, M.C., Zucker, Jean-Daniel, Lehmann, C.U. (ed.), Ammenwerth, E. (ed.), and Nøhr, C. (ed.)

Subjects
nutritional and metabolic diseases, digestive system, digestive system diseases
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a hepatic dis-ease associated with metabolic syndrome. NAFLD covers a spectrum of liver disease from steatosis to non-alcoholic stea-tohepatitis (NASH) and cirrhosis. NASH is a disease evolving under the influence of various stimuli still poorly understood. In this paper we present new clinical decision support system (CDSS) for the diagnosis of NASH and the comparison of this system with machine learn-ing algorithms.

Published
2013

9. Noninvasive diagnosis of nonalcoholic steatohepatitis disease based on clinical decision support system

Author

Douali, N., Abdennour, M., Sasso, M., Miette, V., Tordjman, J., Bedossa, P., Veyrie, N., Poitou, C., Aron-Wisnewsky, J., Clément, K., Jaulent, M.C., Zucker, Jean-Daniel, Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Lehmann, C.U. (ed.), Ammenwerth, E. (ed.), and Nøhr, C. (ed.)

Subjects
nutritional and metabolic diseases, FRANCE, [INFO]Computer Science [cs], digestive system, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, digestive system diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a hepatic dis-ease associated with metabolic syndrome. NAFLD covers a spectrum of liver disease from steatosis to non-alcoholic stea-tohepatitis (NASH) and cirrhosis. NASH is a disease evolving under the influence of various stimuli still poorly understood. In this paper we present new clinical decision support system (CDSS) for the diagnosis of NASH and the comparison of this system with machine learn-ing algorithms.

Published
2013

10. Fibrosis in human adipose tissue : composition, distribution, and link with lipid metabolism and fat mass loss [plus Appendix : Experimental procedures and results]

Author

Divoux, A., Tordjman, J., Lacasa, D., Veyrie, N., Hugol, D., Aissat, A., Basdevant, A., Guerre-Millo, M., Poitou, C., Zucker, Jean-Daniel, Bedossa, P., Clément, K., Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), and Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU)

Subjects
FRANCE, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objective : Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and omental WAT (oWAT) fibrosis in obesity and its relationship with metabolic alterations and surgery-induced weight loss. Research design and methods : Surgical biopsies for scWAT and oWAT were obtained in 65 obese (BMI 48.2 ± 0.8 kg/m(2)) and 9 lean subjects (BMI 22.8 ± 0.7 kg/m(2)). Obese subjects who were candidates for bariatric surgery were clinically characterized before, 3, 6, and 12 months after surgery, including fat mass evaluation by dual energy X-ray absorptiometry. WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry. Results : Fibrosis amount, distribution and collagen types (I, III, and VI) present distinct characteristics in lean and obese subjects and with WAT depots localization (subcutaneous or omental). Obese subjects had more total fibrosis in oWAT and had more pericellular fibrosis around adipocytes than lean subjects in both depots. Macrophages and mastocytes were highly represented in fibrotic bundles in oWAT, whereas scWAT was more frequently characterized by hypocellular fibrosis. The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = -0.30, P = 0.02), and with triglyceride levels (R = -0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05). Importantly, scWAT fibrosis correlated negatively with fat mass loss measured at the three time points after surgery. Conclusions : Our data suggest differential clinical consequences of fibrosis in human WAT. In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

Published
2010

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