FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis.
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.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Ffolliott M
FM
Fisher
Sandra
S
Kleiner
Nicholas
N
Douris
Elliott C
EC
Fox
Rina J
RJ
Mepani
Francisco
F
Verdeguer
Jun
J
Wu
Alexei
A
Kharitonenkov
Jeffrey S
JS
Flier
Eleftheria
E
Maratos-Flier
Bruce M
BM
Spiegelman
D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D052436:Adipose Tissue, White / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003080:Cold Temperature; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012323:RNA Processing, Post-Transcriptional; D022722:Thermogenesis / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors