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Effects of glucagon‐like peptide‐1 on the differentiation and metabolism of human adipocytes
Author(s) -
El Bekay Rajaa,
CoínAragüez Leticia,
FernándezGarcía Diego,
OlivaOlivera Wilfredo,
BernalLópez Rosa,
ClementePostigo Mercedes,
DelgadoLista Javier,
DiazRuiz Alberto,
GuzmanRuiz Rocío,
VázquezMartínez Rafael,
Lhamyani Said,
RocaRodríguez María Mar,
Veledo Sonia Fernandez,
Vendrell Joan,
Malagón María M.,
Tinahones Francisco José
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13481
Subject(s) - endocrinology , medicine , adipose tissue , adipogenesis , adiponectin , adipocyte , exenatide , glucagon like peptide 1 , liraglutide , stromal vascular fraction , receptor , in vivo , type 2 diabetes , insulin , biology , chemistry , insulin resistance , diabetes mellitus , microbiology and biotechnology
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 Ca 2 + concentration ([Ca 2 + ] 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.