Louet, Jean-FrancoisCoste, AgnèsAmazit, LarbiTannour-Louet, MouniaWu, Ray-ChangTsai, Sophia YTsai, Ming-JerAuwerx, JohanO'Malley, Bert W2009-04-022009-04-022009-04-02200610.1073/pnas.0608711103https://infoscience.epfl.ch/handle/20.500.14299/3667117098861The 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.text::journal::journal article::research article