期刊
CELL
卷 148, 期 3, 页码 556-567出版社
CELL PRESS
DOI: 10.1016/j.cell.2011.11.062
关键词
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资金
- Howard Hughes Medical Institute
- NIH [RL1GM084436, R56DK089600, U19DK62434, GM007062]
- Robert A. Welch Foundation [I-1275, I-1558]
- Leona M. and Harry B. Helmsley Charitable Trust
Fibroblast growth factor-21 (FGF21) is a circulating hepatokine that beneficially affects carbohydrate and lipid metabolism. Here, we report that FGF21 is also an inducible, fed-state autocrine factor in adipose tissue that functions in a feed-forward loop to regulate the activity of peroxisome proliferator-activated receptor gamma (PPAR gamma), a master transcriptional regulator of adipogenesis. FGF21 knockout (KO) mice display defects in PPARg signaling including decreased body fat and attenuation of PPAR gamma-dependent gene expression. Moreover, FGF21-KO mice are refractory to both the beneficial insulin-sensitizing effects and the detrimental weight gain and edema side effects of the PPAR gamma agonist rosiglitazone. This loss of function in FGF21-KO mice is coincident with a marked increase in the sumoylation of PPAR gamma, which reduces its transcriptional activity. Adding back FGF21 prevents sumoylation and restores PPAR gamma activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPAR gamma.
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