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The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE79166 | GEO | 2016/07/20

SECONDARY ACCESSION(S): PRJNA315094

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC4865931 | biostudies-literature

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-07-20 | E-GEOD-79166 | biostudies-arrayexpress

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling (Microarray)

Project description:To investigate the role of the transcriptional repressor Rev-erb alpha in epididymal white adipose tissue, we performed a microarray analysis of gene expression in the epididymal white adipose tissue of wildtype and Rev-erb alpha knock-out mice. Examination of the transcriptome in epididymal white adipose tissue of Rev-erb alpha kockout mice compared to wildtype mice.

2016-07-20 | E-GEOD-79164 | biostudies-arrayexpress

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling (Microarray)

2016-07-20 | GSE79164 | GEO

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling (ChIP-seq, eWAT)

Project description:The goal of this study is to identify the cistrome of the transcriptional repressor Rev-erb alpha in epididymal white adipose tissue. Performing Rev-erb alpha ChIP-seq on epididymal white adipose tissue from wildtype mice at 5PM when Rev-erb alpha protein level peaks in wild type (WT) mice, we were able to globally determine the genomic regions undergoing Rev-erb alpha-dependent de-repression. Examination of Rev-erb alpha binding in epididymal white adipose tissue.

2016-07-20 | E-GEOD-79165 | biostudies-arrayexpress

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling (GRO-seq)

Project description:Based upon integrated analysis of transcriptomes and cistromes in Rev-erb alpha knock-out mice, we found that beta-Klotho (KLB) mRNA and protein are markedly induced in white adipose tissue but not in brown adipose tissue or liver of mice lacking Rev-erb alpha. In order to address the mechanism of the tissue-specific regulation of Klb transcription by Rev-erb apha, we performed global run-on followed by high-throughput sequencing (GRO-seq) to measure nascent transcription in different tissues in wildtype mice and Rev-erb alpha knock-out mice.

2016-12-31 | GSE79168 | GEO

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling (ChIP-seq, eWAT)

2016-07-20 | GSE79165 | GEO

The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling

Project description:The Nuclear Receptor Rev-erb alpha Regulates Adipose Tissue-Specific FGF21 Signaling

| PRJNA315094 | ENA

PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis.

Project description:FGF21 is a hormone produced in liver and fat that dramatically improves peripheral insulin sensitivity and lipid metabolism. We show here that obese mice with genetically reduced levels of a key hepatic transcriptional coactivator, PGC-1alpha, have improved whole-body insulin sensitivity with increased levels of hepatic and circulating FGF21. Gain- and loss-of-function studies in primary mouse hepatocytes show that hepatic FGF21 levels are regulated by the expression of PGC-1alpha. Importantly, PGC-1alpha-mediated reduction of FGF21 expression is dependent on Rev-Erbalpha and the expression of ALAS-1. ALAS-1 is a PGC-1alpha target gene and the rate-limiting enzyme in the synthesis of heme, a ligand for Rev-Erbalpha. Modulation of intracellular heme levels mimics the effect of PGC-1alpha on FGF21 expression, and inhibition of heme biosynthesis completely abrogates the down-regulation of FGF21 in response to PGC-1alpha. Thus, PGC-1alpha can impact hepatic and systemic metabolism by regulating the levels of a nuclear receptor ligand.

| S-EPMC2799738 | biostudies-literature

Rev-erb alpha citrome in brown adipose tissue

Project description:We have reported that cold temperature challenge results in a dramatic decrease in levels of the transcriptional repressor, Rev-erb alpha. Performing Rev-erb alpha ChIP-seq on brown adipose from wildtype animals kept at thermoneutrality or cold-challenged (and using Rev-erb alpha KO brown adipose as a control), we were able to globally determine the genomic regions undergoing Rev-erb alpha-dependent de-repression.

2016-12-31 | GSE79167 | GEO

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