Suppression of adipogenesis by valproic acid through repression of USF1-activated fatty acid synthesis in adipocytes

In this study, we identified the molecular mechanism of VPA-mediated suppression of adipogenesis in adipocytes. VPA suppressed the accumulation of intracellular triglycerides. The expression levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α, which are key regulators of adipogenesis, as well as the expression of stearoyl-CoA desaturase, were decreased by the treatment with VPA. Moreover, glycerol release was decreased in the VPA-treated cells; even though the transcription levels of adipose triglyceride lipase, hormone sensitive lipase, and monoacylglycerol lipase, all of which are involved in lipolysis, were elevated by the treatment with VPA. Noteworthily, the expression level of fatty acid synthase (FAS) was significantly suppressed when the cells were cultured in medium containing VPA. Furthermore, VPA-mediated suppression of the accumulation of the intracellular triglycerides was prevented by the treatment with palmitic acid, a major product of FAS. The results of promoter-luciferase and chromatin immunoprecipitation assays demonstrated that upstream stimulating factor 1 (USF1) bound to the E-box of the promoter region of the FAS gene. In addition, the expression of USF1 was decreased by the treatment with VPA. siRNA-mediated knockdown of the expression of the USF1 gene repressed adipogenesis along with the decreased expression of the FAS gene. The overexpression of USF1 enhanced both adipogenesis and the expression ...
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research