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FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis

2012; Cold Spring Harbor Laboratory Press; Volume: 26; Issue: 3 Linguagem: Inglês

10.1101/gad.177857.111

1549-5477

Ffolliott M. Fisher, Sandra Kleiner, Nicholas Douris, Elliott C. Fox, Rina J. Mepani, Francisco Verdeguer, Jun Wu, Alexei Kharitonenkov, Jeffrey S. Flier, Eleftheria Maratos–Flier, Bruce M. Spiegelman,

Lipid metabolism and biosynthesis

Certain white adipose tissue (WAT) depots are readily able to convert to a "brown-like" state with prolonged cold exposure or exposure to β-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1α protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.