| First Author | Jager J | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 20 | Pages | 10867-75 |
| PubMed ID | 27002153 | Mgi Jnum | J:234198 |
| Mgi Id | MGI:5789480 | Doi | 10.1074/jbc.M116.719120 |
| Citation | Jager J, et al. (2016) The Nuclear Receptor Rev-erbalpha Regulates Adipose Tissue-specific FGF21 Signaling. J Biol Chem 291(20):10867-75 |
| abstractText | FGF21 is an atypical member of the FGF family that functions as a hormone to regulate carbohydrate and lipid metabolism. Here we demonstrate that the actions of FGF21 in mouse adipose tissue, but not in liver, are modulated by the nuclear receptor Rev-erbalpha, a potent transcriptional repressor. Interrogation of genes induced in the absence of Rev-erbalpha for Rev-erbalpha-binding sites identified betaKlotho, an essential coreceptor for FGF21, as a direct target gene of Rev-erbalpha in white adipose tissue but not liver. Rev-erbalpha ablation led to the robust elevated expression of betaKlotho. Consequently, the effects of FGF21 were markedly enhanced in the white adipose tissue of mice lacking Rev-erbalpha. A major Rev-erbalpha-controlled enhancer at the Klb locus was also bound by the adipocytic transcription factor peroxisome proliferator-activated receptor (PPAR) gamma, which regulates its activity in the opposite direction. These findings establish Rev-erbalpha as a specific modulator of FGF21 signaling in adipose tissue. |
