title: Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program.
abstract: The white adipocyte is at the center of dysfunctional regulatory pathways in various pathophysiological processes, including obesity, diabetes, inflammation, and cancer. Here, we show that the oncogenic steroid receptor coactivator-3 (SRC-3) is a critical regulator of white adipocyte development. Indeed, in SRC-3(-/-) mouse embryonic fibroblasts, adipocyte differentiation was severely impaired, and reexpression of SRC-3 was able to restore it. The early stages of adipocyte differentiation are accompanied by an increase in nuclear levels of SRC-3, which accumulates to high levels specifically in the nucleus of differentiated fat cells. Moreover, SRC-3(-/-) animals showed reduced body weight and adipose tissue mass with a significant decrease of the expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2), a master gene required for adipogenesis. At the molecular level, SRC-3 acts synergistically with the transcription factor CAAT/enhancer-binding protein to control the gene expression of PPARgamma2. Collectively, these data suggest a crucial role for SRC-3 as an integrator of the complex transcriptional network controlling adipogenesis.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Louet
authors.forename: Agnès
authors.initials: A
authors.lastname: Coste
authors.forename: Larbi
authors.initials: L
authors.lastname: Amazit
authors.forename: Mounia
authors.initials: M
authors.lastname: Tannour-Louet
authors.forename: Ray-Chang
authors.initials: RC
authors.lastname: Wu
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D016475:3T3 Cells; D052438:Adipocytes, White / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056921:Nuclear Receptor Coactivator 3; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D047495:PPAR gamma; D015534:Trans-Activators; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3