title: Peroxisome proliferator-activated receptor-gamma coactivator-1alpha controls transcription of the Sirt3 gene, an essential component of the thermogenic brown adipocyte phenotype.
abstract: 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.
authors: Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, and CIBER Fisiopatologia de la Obesidad y Nutrición, 08028 Barcelona, Spain.
authors: Albert
authors: A
authors: Giralt
authors: Elayne
authors: E
authors: Hondares
authors: Josep A
authors: JA
authors: Villena
authors: Francesc
authors: F
authors: Ribas
authors: Julieta
authors: J
authors: Díaz-Delfín
authors: Marta
authors: M
authors: Giralt
authors: Roser
authors: R
authors: Iglesias
authors: Francesc
authors: F
authors: Villarroya
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000242:Cyclic AMP; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D056566:Sirtuin 3; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C525046:Sirt3 protein, mouse; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1