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Choi, Jang Hyun
Lab of Diabetes and Metabolism (LDM)
Research Interests
  • Diabetes, Metabolic Disorders, PPARg, Gene Regulation, Anti-Diabetic Drug

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Fibroblast Growth Factor-21 Regulates PPAR gamma Activity and the Antidiabetic Actions of Thiazolidinediones

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Title
Fibroblast Growth Factor-21 Regulates PPAR gamma Activity and the Antidiabetic Actions of Thiazolidinediones
Author
Dutchak, Paul A.Katafuchi, TakeshiBookout, Angie L.Choi, Jang HyunYu, Ruth T.Mangelsdorf, David J.Kliewer, Steven A.
Issue Date
2012-02
Publisher
CELL PRESS
Citation
CELL, v.148, no.3, pp.556 - 567
Abstract
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/9465
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84863012459
DOI
10.1016/j.cell.2011.11.062
ISSN
0092-8674
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