Glucagon Is Essential for Adaptive Thermogenesis in Brown Adipose Tissue

• DOI: 10.1210/en.2014-1175
• Publication Date: 2014-06-20T13:36:25Z
• Authors: Keita Kinoshita; Nobuaki Ozaki; Yusuke Takagi; Yoshiharu Murata; Yoshiharu Oshida; Yoshitaka Hayashi
• Keywords: FGF21; Thermogenin; Glucagon receptor

Glucagon, a counterregulatory hormone to insulin, serves as regulator of glucose homeostasis and acts in response hypoglycemia. Earlier studies have shown that glucagon administration induces thermogenesis experimental animal models. However, it is not known whether endogenous involved the regulation brown adipose tissue (BAT) function. Here we investigated role cold-induced male mice deficient proglucagon-derived peptides (GCGKO mice). Upon exposure cold, GCGKO exhibited greater decrease rectal temperature than control mice. The cold exposure-induced increase oxygen consumption was less seen Moreover, after β3-adrenergic receptor agonist, CL-316,243, also lesser Expression thermogenic genes, including gene encoding uncoupling protein 1 (Ucp1), reduced BAT under ambient well conditions. Administration restored expression Ucp1 mRNA fibroblast growth factor 21 (Fgf21) liver. Supplementation with for 2 weeks resulted higher plasma Fgf21 levels improved responses CL-316,243 These results indicated essential adaptive regulates function, most likely by increasing hepatic production.