| First Author | Ohoka N | Year | 2009 |
| Journal | Mol Endocrinol | Volume | 23 |
| Issue | 6 | Pages | 759-71 |
| PubMed ID | 19324970 | Mgi Jnum | J:148702 |
| Mgi Id | MGI:3846256 | Doi | 10.1210/me.2008-0277 |
| Citation | Ohoka N, et al. (2009) The orphan nuclear receptor ROR{alpha} restrains adipocyte differentiation through a reduction of C/EBP{beta} activity and perilipin gene expression. Mol Endocrinol 23(6):759-71 |
| abstractText | 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. |
