RRC ID 21513
Author Ohoka N, Kato S, Takahashi Y, Hayashi H, Sato R.
Title The orphan nuclear receptor RORalpha restrains adipocyte differentiation through a reduction of C/EBPbeta activity and perilipin gene expression.
Journal Mol Endocrinol
Abstract The nuclear receptor-type transcription factor retinoic acid receptor-related orphan receptor alpha (RORalpha) is a multifunctional molecule involved in tissue development and cellular function, such as inflammation, metabolism, and differentiation; however, the role of RORalpha during adipocyte differentiation has not yet been fully understood. Here we show that RORalpha inhibits the transcriptional activity of CCAAT/enhancer-binding protein beta (C/EBPbeta) without affecting its expression, thereby blocking the induction of both PPARgamma and C/EBPalpha, resulting in the suppression of C/EBPbeta-dependent adipogenesis. RORalpha interacted with C/EBPbeta so as to repress both the C/EBPbeta-p300 association and the C/EBPbeta-dependent recruitment of p300 to chromatin. In addition to the inhibitory effect on C/EBPbeta function, RORalpha also prevents the expression of the lipid droplet coating protein gene perilipin by peroxisome proliferators-activated receptor gamma (PPARgamma), acting through the specific mechanism of its promoter. We identified a suppressive ROR-responsive element overlapping the PPAR-responsive element in the perilipin promoter and verified that RORalpha competitively antagonizes the binding of PPARgamma. RORalpha inhibits PPARgamma-dependent adipogenesis along with the repression of perilipin induction. These findings suggest that RORalpha is a novel negative regulator of adipocyte differentiation that acts through dual mechanisms.
Volume 23(6)
Pages 759-71
Published 2009-6-1
DOI 10.1210/me.2008-0277
PII me.2008-0277
PMID 19324970
PMC PMC5419281
MeSH 3T3-L1 Cells Adipocytes / cytology* Adipocytes / metabolism* Adipogenesis / genetics Animals CCAAT-Enhancer-Binding Protein-beta / genetics CCAAT-Enhancer-Binding Protein-beta / metabolism* Carrier Proteins Cell Differentiation / genetics* Chromatin / metabolism DNA / metabolism E1A-Associated p300 Protein / metabolism Gene Expression Regulation* Gene Knockdown Techniques Mice Nuclear Receptor Subfamily 1, Group F, Member 1 PPAR gamma / metabolism Perilipin-1 Phosphoproteins / genetics* Phosphoproteins / metabolism Phosphorylation Promoter Regions, Genetic / genetics Protein Binding Receptors, Cytoplasmic and Nuclear / metabolism* Trans-Activators / metabolism* Transcription, Genetic
IF 3.628
Times Cited 32
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) CS-RfA-EG (RDB04391) pCAG-HIVgp (RDB04394) pENTR4-H1 (RDB04395) pCMV-VSV-G-RSV-Rev (RDB04393)