BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.
BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: 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. KEY RESULTS:GLP-1 down-regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obesepatients. 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. CONCLUSIONS AND IMPLICATIONS: 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.
Authors: Michael J Curtis; Richard A Bond; Domenico Spina; Amrita Ahluwalia; Stephen P A Alexander; Mark A Giembycz; Annette Gilchrist; Daniel Hoyer; Paul A Insel; Angelo A Izzo; Andrew J Lawrence; David J MacEwan; Lawrence D F Moon; Sue Wonnacott; Arthur H Weston; John C McGrath Journal: Br J Pharmacol Date: 2015-07 Impact factor: 8.739
Authors: Yi Wang; Keunpoong Lim; Marc Normandin; Xiaojian Zhao; Gary W Cline; Yu-Shin Ding Journal: Nucl Med Biol Date: 2011-10-26 Impact factor: 2.408
Authors: Joan Vendrell; Rajaa El Bekay; Belén Peral; Eduardo García-Fuentes; Anna Megia; Manuel Macias-Gonzalez; José Fernández Real; Yolanda Jimenez-Gomez; Xavier Escoté; Gisela Pachón; Rafael Simó; David M Selva; María M Malagón; Francisco J Tinahones Journal: Endocrinology Date: 2011-08-23 Impact factor: 4.736
Authors: Ahmed M Elmansi; Mohamed E Awad; Nada H Eisa; Dmitry Kondrikov; Khaled A Hussein; Alexandra Aguilar-Pérez; Samuel Herberg; Sudharsan Periyasamy-Thandavan; Sadanand Fulzele; Mark W Hamrick; Meghan E McGee-Lawrence; Carlos M Isales; Brian F Volkman; William D Hill Journal: Pharmacol Ther Date: 2019-02-10 Impact factor: 12.310
Authors: Rajaa El Bekay; Leticia Coín-Aragüez; Diego Fernández-García; Wilfredo Oliva-Olivera; Rosa Bernal-López; Mercedes Clemente-Postigo; Javier Delgado-Lista; Alberto Diaz-Ruiz; Rocío Guzman-Ruiz; Rafael Vázquez-Martínez; Said Lhamyani; María Mar Roca-Rodríguez; Sonia Fernandez Veledo; Joan Vendrell; María M Malagón; Francisco José Tinahones Journal: Br J Pharmacol Date: 2016-04-28 Impact factor: 8.739
Authors: Huub J van Eyk; Elisabeth H M Paiman; Maurice B Bizino; Paul de Heer; Petronella H Geelhoed-Duijvestijn; Aan V Kharagjitsingh; Johannes W A Smit; Hildo J Lamb; Patrick C N Rensen; Ingrid M Jazet Journal: Cardiovasc Diabetol Date: 2019-07-09 Impact factor: 9.951
Authors: Fernanda C B Oliveira; Eduarda J Bauer; Carolina M Ribeiro; Sidney A Pereira; Bruna T S Beserra; Simone M Wajner; Ana L Maia; Francisco A R Neves; Michella S Coelho; Angelica A Amato Journal: Front Endocrinol (Lausanne) Date: 2022-01-04 Impact factor: 5.555