| First Author | Dutchak PA | Year | 2012 |
| Journal | Cell | Volume | 148 |
| Issue | 3 | Pages | 556-67 |
| PubMed ID | 22304921 | Mgi Jnum | J:181335 |
| Mgi Id | MGI:5311059 | Doi | 10.1016/j.cell.2011.11.062 |
| Citation | Dutchak PA, et al. (2012) Fibroblast growth factor-21 regulates PPARgamma activity and the antidiabetic actions of thiazolidinediones. Cell 148(3):556-67 |
| abstractText | 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 (PPARgamma), a master transcriptional regulator of adipogenesis. FGF21 knockout (KO) mice display defects in PPARgamma signaling including decreased body fat and attenuation of PPARgamma-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 PPARgamma agonist rosiglitazone. This loss of function in FGF21-KO mice is coincident with a marked increase in the sumoylation of PPARgamma, which reduces its transcriptional activity. Adding back FGF21 prevents sumoylation and restores PPARgamma activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPARgamma. |
