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

The Biochemical journal (2014-02-12)
Miki Yuyama, Ko Fujimori
RESUMEN

VPA (valproic acid), a short-chain fatty acid that is a HDAC (histone deacetylase) inhibitor, is known to suppress adipogenesis. In the present study, we identified the molecular mechanism of VPA-mediated suppression of adipogenesis in adipocytes. VPA suppressed the accumulation of intracellular triacylglycerol. The expression levels of PPARγ (peroxisome-proliferator-activated receptor γ) and C/EBPα (CCAAT/enhancer-binding protein α), which are key regulators of adipogenesis, as well as the expression of SCD (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 ATGL (adipose triacylglycerol lipase), HSL (hormone-sensitive lipase) and MGL (monoacylglycerol lipase), all of which are involved in lipolysis, were elevated by the treatment with VPA. It is noteworthy that the expression level of FAS (fatty acid synthase) was significantly suppressed when the cells were cultured in medium containing VPA. Furthermore, VPA-mediated suppression of the accumulation of the intracellular triacylglycerols was prevented by the treatment with palmitic acid, a major product of FAS. The results of promoter-luciferase and chromatin immunoprecipitation assays demonstrated that USF1(upstream stimulating factor 1) 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 of FAS in VPA-treated cells. These results indicate that VPA suppressed adipogenesis through the down-regulation of USF1-activated fatty acid synthesis in adipocytes.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Palmitic acid, ≥99%
Supelco
Valproic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Palmitic acid, BioXtra, ≥99%
Supelco
Palmitic acid, analytical standard
Supelco
Palmitic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Palmitic acid, ≥95%, FCC, FG
Sigma-Aldrich
Palmitic acid, natural, 98%, FG
USP
Palmitic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Palmitic acid, ≥98% palmitic acid basis (GC)
Palmitic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
2-Propylpentanoic acid
USP
Valproic acid, United States Pharmacopeia (USP) Reference Standard
Valproic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Palmitic acid, certified reference material, TraceCERT®