| 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
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| DNA material |
CSII-EF-MCS-IRES2-Venus (RDB04384)
CS-RfA-EG (RDB04391)
pCAG-HIVgp (RDB04394)
pENTR4-H1 (RDB04395)
pCMV-VSV-G-RSV-Rev (RDB04393) |
