| First Author | Giralt A | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 19 | Pages | 16958-66 |
| PubMed ID | 21454513 | Mgi Jnum | J:172686 |
| Mgi Id | MGI:5008534 | Doi | 10.1074/jbc.M110.202390 |
| Citation | Giralt A, et al. (2011) Peroxisome Proliferator-activated Receptor-{gamma} Coactivator-1{alpha} Controls Transcription of the Sirt3 Gene, an Essential Component of the Thermogenic Brown Adipocyte Phenotype. J Biol Chem 286(19):16958-66 |
| abstractText | Sirt3 (silent mating type information regulation 2, homolog 3), a member of the sirtuin family of protein deacetylases with multiple actions on metabolism and gene expression is expressed in association with brown adipocyte differentiation. Using Sirt3-null brown adipocytes, we determined that Sirt3 is required for an appropriate responsiveness of cells to noradrenergic, cAMP-mediated activation of the expression of brown adipose tissue thermogenic genes. The transcriptional coactivator Pgc-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) induced Sirt3 gene expression in white adipocytes and embryonic fibroblasts as part of its overall induction of a brown adipose tissue-specific pattern of gene expression. In cells lacking Sirt3, Pgc-1alpha failed to fully induce the expression of brown fat-specific thermogenic genes. Pgc-1alpha activates Sirt3 gene transcription through coactivation of the orphan nuclear receptor Err (estrogen-related receptor)-alpha, which bound the proximal Sirt3 gene promoter region. Erralpha knockdown assays indicated that Erralpha is required for full induction of Sirt3 gene expression in response to Pgc-1alpha. The present results indicate that Pgc-1alpha controls Sirt3 gene expression and this action is an essential component of the overall mechanisms by which Pgc-1alpha induces the full acquisition of a brown adipocyte differentiated phenotype. |
