Effects of a fatty acid synthase inhibitor on adipocyte differentiation of mouse 3T3-L1 cells.
OBJECTIVE
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).


CONCLUSIONS
C75 blocked the adipocyte differentiation, which was related with down-regulation of PPARgamma mRNA.
Liu
Li-Hong
LH
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Wang
Xiao-Kui
XK
Hu
Yuan-Dong
YD
Kang
Jian-Lei
JL
Wang
Li-Li
LL
Li
Song
S
D016475:3T3 Cells / Q000187:drug effects; D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005786:Gene Expression Regulation; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D047495:PPAR gamma; D012333:RNA, Messenger; D005993:Glycerolphosphate Dehydrogenase; D064429:Fatty Acid Synthases; D015107:4-Butyrolactone