title: GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1.
abstract: OBJECTIVE
  Accumulating evidence has revealed the significant role of glucagon-like peptide-1 (GLP-1) in weight loss. Sirtuin 1 (SIRT1) plays a vital role in the regulation of lipid metabolism. Here, we investigated the contribution of lipolytic and oxidative changes in white adipose tissue (WAT) to the weight-lowering effect induced by the GLP-1 receptor (GLP-1R) agonist exenatide (exendin-4) in mice. We also looked at the role of SIRT1 in this process.
  
  
  METHODS
  C57BL/6J mice and Sirt1 (+/-) mice were treated with exenatide (24 nmol/kg) or an NaCl solution (154 mmol/l) control i.p. for 8 weeks while receiving a high-fat diet (HFD) after a 12 week HFD challenge. Systemic phenotypic evaluations were carried out during and after the intervention. A lentivirus-mediated short hairpin (sh)RNA vector of the Sirt1 gene was transfected into differentiated 3T3-L1 adipocytes. An in vitro model system used adipocytes induced from Sirt1-null mouse embryonic fibroblasts (MEFs).
  
  
  RESULTS
  Exenatide reduced fat mass and enhanced the lipolytic and oxidative capacity of WAT in diet-induced obese C57BL/6J mice. However, these effects were significantly impaired in Sirt1 (+/-) mice compared with wild-type controls. In vitro, exendin-4 increased lipolysis and fatty acid oxidation by upregulating SIRT1 expression and activity in differentiated 3T3-L1 adipocytes. Conversely, RNA interference (i)-induced knockdown of SIRT1 attenuated the lipolytic and oxidative responses to exendin-4 in differentiated 3T3-L1 adipocytes. Again, these responses were entirely abolished in Sirt1-null MEFs after induction into adipocytes.
  
  
  CONCLUSIONS
  These data highlight that a GLP-1R agonist promotes brown remodelling of WAT in a SIRT1-dependent manner; this might be one of the mechanisms underlying its effect on weight loss.
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Fen
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Beisi
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Zonglan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Huanyi
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China. wjianp@mail.sysu.edu.cn.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, People's Republic of China. wjianp@mail.sysu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D010455:Peptides / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D056564:Sirtuin 1; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Adipocytes; Fatty acid oxidation; GLP-1; Lipolysis; Obesity; Sirtuin 1