RT Journal Article T1 Effects of glucagon-like peptide-1 on the differentiation and metabolism of human adipocytes. A1 El Bekay, Rajaa A1 Coin-Aragüez, Leticia A1 Fernandez-Garcia, Diego A1 Oliva-Olivera, Wilfredo A1 Bernal-Lopez, Rosa A1 Clemente-Postigo, Mercedes A1 Delgado-Lista, Javier A1 Diaz-Ruiz, Alberto A1 Guzman-Ruiz, Rocio A1 Vazquez-Martinez, Rafael A1 Lhamyani, Said A1 Roca-Rodriguez, Maria Mar A1 Veledo, Sonia Fernandez A1 Vendrell, Joan A1 Malagon, Maria M A1 Tinahones, Francisco Jose K1 3T3-L1 cells K1 Adipocytes K1 Animals K1 Cell differentiation K1 Diabetes mellitus, type 2 AB Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP-1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up-regulated in AT of insulin-resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP-1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects. We analysed the effects of GLP-1 on human AT and isolated adipocytes in vitro and the effects of GLP-1 mimetics on AT of morbidly obese T2D subjects in vivo. GLP-1 down-regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obese patients. GLP-1 also decreased the expression of adipogenic/lipogenic genes in AT explants and mature adipocytes, while increasing that of lipolytic markers and adiponectin. In 3T3-L1 adipocytes, GLP-1 decreased free cytosolic Ca2+ concentration ([Ca2+]i). GLP-1-induced responses were only partially blocked by GLP-1 receptor antagonist exendin (9–39). Moreover, administration of exenatide or liraglutide reduced adipogenic and inflammatory marker mRNA in AT of T2D obese subjects. Our data suggest that the beneficial effects of GLP-1 are associated with changes in the adipogenic potential and ability of AT to expand, via activation of the canonical GLP-1 receptor and an additional, as yet unknown, receptor. PB John Wiley & Sons YR 2016 FD 2016-02-29 LK http://hdl.handle.net/10668/9931 UL http://hdl.handle.net/10668/9931 LA en NO El Bekay R, Coín-Aragüez L, Fernández-García D, Oliva-Olivera W, Bernal-López R, Clemente-Postigo M, et al. Effects of glucagon-like peptide-1 on the differentiation and metabolism of human adipocytes. Br J Pharmacol. 2016 Jun;173(11):1820-34 NO Thiswork was supported by grants from the Spanish Ministry ofHealth (FIS) (PI12/02355, PS09/00997 and PI13/02628), theConsejería de Innovación and co-funded by Fondo Europeo deDesarrollo Regional–FEDER (CTS04369, CTS-03039, PI11-CTS-8181 and PI11-CTS-7895) and the Ministerio de Economía yCompetitividad and co-funded by Fondo Europeo de DesarrolloRegional–FEDER (BFU2010–17116). Rajaa El Bekay is recipientof a post-doctoral grant ‘Miguel Servet II’ (CPII13/00041) fromthe Spanish Ministry of Health. CIBERobn is an initiative of ISCIII(Instituto de Salud Carlos III), Spain. M.C.P. was recipient of a FPUgrant from the Ministry of Education (Spain) (AP2009–4537) DS RISalud RD Apr 8, 2025