The Nuclear Receptor Rev-erb? Regulates Adipose Tissue-specific FGF21 Signaling.

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-erb?, a potent transcriptional repressor. Interrogation of genes induced in the absence of Rev-erb? for Rev-erb?-binding sites identified ?Klotho, an essential coreceptor for FGF21, as a direct target gene of Rev-erb? in white adipose tissue but not liver. Rev-erb? ablation led to the robust elevated expression of ?Klotho. Consequently, the effects of FGF21 were markedly enhanced in the white adipose tissue of mice lacking Rev-erb?. A major Rev-erb?-controlled enhancer at the Klb locus was also bound by the adipocytic transcription factor peroxisome proliferator-activated receptor (PPAR) ?, which regulates its activity in the opposite direction. These findings establish Rev-erb? as a specific modulator of FGF21 signaling in adipose tissue.

SUBMITTER: Jager J 

PROVIDER: S-EPMC4865931 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature