Open AccessOncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program
Author(s) -
Jean-François Louet,
Agnès Coste,
Larbi Amazit,
Mounia TannourLouet,
Ray-Chang Wu,
Sophia Y. Tsai,
MingJer Tsai,
Johan Auwerx,
Bert W. O’Malley
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0608711103
Subject(s) - adipogenesis , biology , coactivator , adipocyte , endocrinology , nuclear receptor coactivator 1 , regulator , medicine , microbiology and biotechnology , white adipose tissue , transcription factor , nuclear receptor , adipose tissue , genetics , gene
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.