Glucagon Is Essential for Adaptive Thermogenesis in Brown Adipose Tissue

Glucagon, a counterregulatory hormone to insulin, serves as a regulator of glucose homeostasis and acts in response to hypoglycemia. Earlier studies have shown that glucagon administration induces thermogenesis in experimental animal models. However, it is not known whether endogenous glucagon is involved in the regulation of brown adipose tissue (BAT) function. Here we investigated the role of glucagon in cold-induced thermogenesis in male mice deficient in proglucagon-derived peptides (GCGKO mice). Upon exposure to cold, GCGKO mice exhibited a greater decrease in rectal temperature than control mice. The cold exposure-induced increase in oxygen consumption in GCGKO mice was less than that seen in control mice. Moreover, the increase in oxygen consumption after administration of a β3-adrenergic receptor agonist, CL-316,243, was also lesser in GCGKO than in control mice. Expression of thermogenic genes, including the gene encoding uncoupling protein 1 (Ucp1), was reduced in the BAT of GCGKO mice under amb...