Peroxisome Proliferator-activated Receptor-γ Coactivator-1α Controls Transcription of the Sirt3 Gene, an Essential Component of the Thermogenic Brown Adipocyte Phenotype

• Published in: The Journal of biological chemistry Vol. 286; no. 19; pp. 16958 - 16966
• Main Authors: Giralt, Albert, Hondares, Elayne, Villena, Josep A., Ribas, Francesc, Díaz-Delfín, Julieta, Giralt, Marta, Iglesias, Roser, Villarroya, Francesc
• Format: Journal Article
• Language: English
• Published: 9650 Rockville Pike, Bethesda, MD 20814, U.S.A Elsevier Inc 13.05.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Adipocyte; Adipose Tissue; Adipose Tissue Metabolism; Brown Adipose Tissue; Gene Regulation; Sirtuins; Thermogenesis; Transcription Coactivators; Uncoupling Protein; Sirtuins; Transcription Coactivators; Adipocyte; Adipose Tissue Metabolism; Thermogenesis; Brown Adipose Tissue; Uncoupling Protein; Adipose Tissue
• DOI: 10.1074/jbc.M110.202390
• ISSN: 0021-9258

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-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) 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-1α failed to fully induce the expression of brown fat-specific thermogenic genes. Pgc-1α activates Sirt3 gene transcription through coactivation of the orphan nuclear receptor Err (estrogen-related receptor)-α, which bound the proximal Sirt3 gene promoter region. Errα knockdown assays indicated that Errα is required for full induction of Sirt3 gene expression in response to Pgc-1α. The present results indicate that Pgc-1α controls Sirt3 gene expression and this action is an essential component of the overall mechanisms by which Pgc-1α induces the full acquisition of a brown adipocyte differentiated phenotype.