title: Effects of glucagon-like peptide-1 on the differentiation and metabolism of human adipocytes.
abstract: 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.
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: Rajaa
authors.initials: R
authors.lastname: El Bekay
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Coín-Aragüez
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Endocrinology Service, Virgen de la Victoria Clinical University Hospital, Malaga, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Fernández-García
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Oliva-Olivera
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bernal-López
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Clemente-Postigo
authors.affiliation: Lipids and Atherosclerosis Unit, Department of Medicine, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, IMIBIC/Reina Sofia University Hospital/Universidad de Cordoba, CIBERobn, Córdoba, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Diaz-Ruiz
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, IMIBIC/Reina Sofia University Hospital/Universidad de Cordoba, CIBERobn, Córdoba, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Guzman-Ruiz
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, IMIBIC/Reina Sofia University Hospital/Universidad de Cordoba, CIBERobn, Córdoba, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vázquez-Martínez
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: Said
authors.initials: S
authors.lastname: Lhamyani
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Laboratory of Biomedical Research, Virgen de la Victoria Clinical University Hospital, Málaga, Spain.
authors.forename: María Mar
authors.initials: MM
authors.lastname: Roca-Rodríguez
authors.affiliation: CIBERDEM, Joan XXIII University Hospital, Pere Virgili Institute, Tarragona, Spain.
authors.forename: Sonia Fernandez
authors.initials: SF
authors.lastname: Veledo
authors.affiliation: CIBERDEM, Joan XXIII University Hospital, Pere Virgili Institute, Tarragona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, IMIBIC/Reina Sofia University Hospital/Universidad de Cordoba, CIBERobn, Córdoba, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.affiliation: CIBER Pathophysiology of Obesity and Nutrition CB06/03, Carlos III Health Institute, Malaga, Spain.|Endocrinology Service, Virgen de la Victoria Clinical University Hospital, Malaga, Spain.
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Tinahones
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D000077270:Exenatide; D015870:Gene Expression / Q000187:drug effects; D005819:Genetic Markers; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000627:therapeutic use; D010865:Pilot Projects; D011446:Prospective Studies; D014688:Venoms / Q000627:therapeutic use
chemical_list: D005819:Genetic Markers; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide