Effects of a Fatty Acid Synthase Inhibitor on Adipocyte Differentiation of Mouse 3T3-L1 Cells

Acta Pharmacol Sin. 2004 Aug;25(8):1052-7.

Abstract

Aim: To investigate the influence of C75, a fatty acid synthase inhibitor, on adipocyte differentiation.

Methods: Mouse 3T3-L1 preadipocytes were induced to differentiation by insulin, isobutylmethylxanthine, and dexamethasone. Oil red O staining was performed and activity of glycerol-3-phosphate dehydrogenase (GPDH) was measured. The level of peroxisome proliferators-activated receptor gamma (PPARgamma) mRNA was assayed by semi-quantitative reverse transcription PCR.

Results: C75 blocked the adipogenic conversion in a dose-dependent manner and the inhibitory effects occurred both in the early phases (48 h) and in the latter phases (8 d) of the process. Treatment with C75 for 8 d induced more decrease in lipid content than 48 h (P<0.01). Treatment with C75 50 mg/L for 48 h or 8 d decreased GPDH activity by 52.8 % and 31.2 % of Vehicle, respectively. Treatment with C75 10-50 mg/L for 48 h or 8 d down-regulated PPARgamma mRNA expression compared with control (P<0.01).

Conclusion: C75 blocked the adipocyte differentiation, which was related with down-regulation of PPARgamma mRNA.

MeSH terms

  • 3T3 Cells / drug effects
  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology*
  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Down-Regulation
  • Fatty Acid Synthases / antagonists & inhibitors*
  • Fatty Acid Synthases / metabolism
  • Gene Expression Regulation
  • Glycerolphosphate Dehydrogenase / metabolism*
  • Mice
  • PPAR gamma / biosynthesis*
  • PPAR gamma / genetics
  • RNA, Messenger / genetics

Substances

  • 4-methylene-2-octyl-5-oxofuran-3-carboxylic acid
  • PPAR gamma
  • RNA, Messenger
  • Glycerolphosphate Dehydrogenase
  • Fatty Acid Synthases
  • 4-Butyrolactone