Yuejun Liu1, Judith Aron-Wisnewsky1, Geneviève Marcelin1, Laurent Genser1, Gilles Le Naour1, Adriana Torcivia1, Brigitte Bauvois1, Sandrine Bouchet1, Véronique Pelloux1, Magali Sasso1, Véronique Miette1, Joan Tordjman1, Karine Clément1. 1. Institute of Cardiometabolism and Nutrition (ICAN) (Y.L., J.A.-W., G.M., L.G., V.P., J.T., K.C.), INSERM (Y.L., J.A.-W., G.M., L.G., V.P., J.T., K.C.), Unité Mixte de Recherche en Santé 1166, Nutriomic Team 6; Departments of Nutrition (J.A.-W., K.C.) and Digestive and Hepato-Pancreato-Biliary Surgery (L.G., A.T.), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital; Department of Pathology (G.L.N.), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Unité d'Imagerie Numérique Morphologique en Anatomo-Pathologie, Université Pierre et Marie Curie, F-75013 Paris, France; Unité Mixte de Recherche en Santé 1166 (Y.L., J.A.-W., G.M., L.G., V.P., J.T., K.C.), Sorbonne Universités, Université Pierre et Marie Curie Paris 06, F-75005, Paris, France; Research Department of Echosens company (Y.L., M.S., V.M.), 75013, Paris, France; Centre de Recherche des Cordeliers (B.B., S.B.), INSERM Unité Mixte de Recherche en Santé 1138, Sorbonne Universités, Université Pierre et Marie Curie, and Université Paris Descartes Sorbonne Paris Cité, F-75006 Paris, France.
Abstract
CONTEXT: Extracellular matrix (ECM) in sc adipose tissue (scAT) undergoes pathological remodeling during obesity. However, its evolution during weight loss remains poorly explored. OBJECTIVE: The objective of the investigation was to study the histological, transcriptomic, and physical characteristics of scAT ECM remodeling during the first year of bariatric surgery (BS)-induced weight loss and their relationships with metabolic and bioclinical improvements. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: A total of 118 morbidly obese candidates for BS were recruited and followed up during 1 year after BS. MAIN OUTCOME MEASURES: scAT surgical biopsy and needle aspiration as well as scAT stiffness measurement were performed in three subgroups before and after BS. Fourteen nonobese, nondiabetic subjects served as controls. RESULTS: Significantly increased picrosirius-red-stained collagen accumulation in scAT after BS was observed along with fat mass loss, despite metabolic and inflammatory improvements and undetectable changes of scAT stiffness. Collagen accumulation positively associated with M2-macrophages (CD163(+) cells) before BS but negatively afterward. Expression levels of genes encoding ECM components (eg, COL3A1, COL6A1, COL6A2, ELN), cross-linking enzymes (eg, lysyl oxidase [LOX], LOXL4, transglutaminase), metalloproteinases, and their inhibitors were modified 1 year after BS. LOX expression and protein were significantly decreased and associated with decreased fat mass as well as other cross-linking enzymes. Although total collagen I and VI staining decreased 1 year after BS, we found increased degraded collagen I and III in scAT, suggesting increased degradation. CONCLUSIONS: After BS-induced weight loss and related metabolic improvements, scAT displays major collagen remodeling with an increased picrosirius-red staining that relates to increased collagen degradation and importantly decreased cross-linking. These features are in agreement with adequate ECM adaptation during fat mass loss.
CONTEXT: Extracellular matrix (ECM) in sc adipose tissue (scAT) undergoes pathological remodeling during obesity. However, its evolution during weight loss remains poorly explored. OBJECTIVE: The objective of the investigation was to study the histological, transcriptomic, and physical characteristics of scAT ECM remodeling during the first year of bariatric surgery (BS)-induced weight loss and their relationships with metabolic and bioclinical improvements. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: A total of 118 morbidly obese candidates for BS were recruited and followed up during 1 year after BS. MAIN OUTCOME MEASURES: scAT surgical biopsy and needle aspiration as well as scAT stiffness measurement were performed in three subgroups before and after BS. Fourteen nonobese, nondiabetic subjects served as controls. RESULTS: Significantly increased picrosirius-red-stained collagen accumulation in scAT after BS was observed along with fat mass loss, despite metabolic and inflammatory improvements and undetectable changes of scAT stiffness. Collagen accumulation positively associated with M2-macrophages (CD163(+) cells) before BS but negatively afterward. Expression levels of genes encoding ECM components (eg, COL3A1, COL6A1, COL6A2, ELN), cross-linking enzymes (eg, lysyl oxidase [LOX], LOXL4, transglutaminase), metalloproteinases, and their inhibitors were modified 1 year after BS. LOX expression and protein were significantly decreased and associated with decreased fat mass as well as other cross-linking enzymes. Although total collagen I and VI staining decreased 1 year after BS, we found increased degraded collagen I and III in scAT, suggesting increased degradation. CONCLUSIONS: After BS-induced weight loss and related metabolic improvements, scAT displays major collagen remodeling with an increased picrosirius-red staining that relates to increased collagen degradation and importantly decreased cross-linking. These features are in agreement with adequate ECM adaptation during fat mass loss.
Authors: Charmaine S Tam; Leanne M Redman; Frank Greenway; Karl A LeBlanc; Mark G Haussmann; Eric Ravussin Journal: J Clin Endocrinol Metab Date: 2016-08-04 Impact factor: 5.958
Authors: A Michaud; J Tordjman; M Pelletier; Y Liu; S Laforest; S Noël; G Le Naour; C Bouchard; K Clément; A Tchernof Journal: Int J Obes (Lond) Date: 2016-10-04 Impact factor: 5.095
Authors: Liske M Kotzé-Hörstmann; Dheshnie Keswell; Kevin Adams; Thandiwe Dlamini; Julia H Goedecke Journal: Endocrine Date: 2016-09-14 Impact factor: 3.633