Abstract
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-erbα, a potent transcriptional repressor. Interrogation of genes induced in the absence of Rev-erbα for Rev-erbα-binding sites identified βKlotho, an essential coreceptor for FGF21, as a direct target gene of Rev-erbα in white adipose tissue but not liver. Rev-erbα ablation led to the robust elevated expression of βKlotho. Consequently, the effects of FGF21 were markedly enhanced in the white adipose tissue of mice lacking Rev-erbα. A major Rev-erbα-controlled enhancer at the Klb locus was also bound by the adipocytic transcription factor peroxisome proliferator-activated receptor (PPAR) γ, which regulates its activity in the opposite direction. These findings establish Rev-erbα as a specific modulator of FGF21 signaling in adipose tissue.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | The Journal of Biological Chemistry |
| Vol/bind | 291 |
| Udgave nummer | 20 |
| Sider (fra-til) | 10867-75 |
| Antal sider | 9 |
| ISSN | 0021-9258 |
| DOI | |
| Status | Udgivet - 13 maj 2016 |
| Udgivet eksternt | Ja |