M Poggi1, S O Morin2, D Bastelica1, R Govers1, M Canault1, D Bernot1, O Georgelin1, M Verdier1, R Burcelin3, D Olive2, M-C Alessi1, F Peiretti1, J A Nunès2. 1. 1] Inserm, U1062, Marseilles, France [2] Inra, UMR1260, Marseilles, France [3] Aix-Marseille Université, NORT, Marseilles, France. 2. 1] Inserm, U1068, CRCM, Marseilles, France [2] Institut Paoli-Calmettes, Marseilles, France [3] Aix-Marseille Université, UM 105, Marseilles, France [4] CNRS, UMR7258, CRCM, Marseilles, France. 3. 1] Inserm, U1048, Toulouse, France [2] Université Paul Sabatier, IMC, Toulouse Cedex 4, France.
Abstract
BACKGROUND/ OBJECTIVES: Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown. METHODS: During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions. RESULTS: Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation. CONCLUSIONS: Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.
BACKGROUND/ OBJECTIVES: Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown. METHODS: During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions. RESULTS:Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation. CONCLUSIONS: Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.
Authors: Vincenzo Mirenda; Sarah J Jarmin; Rachel David; Julian Dyson; Diane Scott; Yan Gu; Robert I Lechler; Klaus Okkenhaug; Federica M Marelli-Berg Journal: Blood Date: 2007-04-01 Impact factor: 22.113
Authors: J Amar; M Serino; C Lange; C Chabo; J Iacovoni; S Mondot; P Lepage; C Klopp; J Mariette; O Bouchez; L Perez; M Courtney; M Marre; P Klopp; O Lantieri; J Doré; M A Charles; B Balkau; R Burcelin Journal: Diabetologia Date: 2011-12 Impact factor: 10.122
Authors: Ulrich Kintscher; Martin Hartge; Katharina Hess; Anna Foryst-Ludwig; Markus Clemenz; Martin Wabitsch; Pamela Fischer-Posovszky; Thomas F E Barth; Duska Dragun; Thomas Skurk; Hans Hauner; Matthias Blüher; Thomas Unger; Anna-Maria Wolf; Uwe Knippschild; Vinzenz Hombach; Nikolaus Marx Journal: Arterioscler Thromb Vasc Biol Date: 2008-04-17 Impact factor: 8.311
Authors: Marina Nati; David Haddad; Andreas L Birkenfeld; Christian A Koch; Triantafyllos Chavakis; Antonios Chatzigeorgiou Journal: Rev Endocr Metab Disord Date: 2016-03 Impact factor: 6.514
Authors: Mira Horváthová; Silvia Ilavská; Kornélia Štefíková; Michaela Szabová; Zora Krivošíková; Eva Jahnová; Jana Tulinská; Viera Spustová; Martin Gajdoš Journal: Int J Environ Res Public Health Date: 2017-07-11 Impact factor: 3.390