Caffeic Acid Phenethyl Ester Inhibits Lipid Accumulation Through Tgf-?/smad Signaling Pathway In 3t3-l1 Adipocytes

[Objective]To investigate the inhibitory effect of caffeic acid phenethyl ester(CAPE)on the differentiation of 3T3-L1 mouse fibroblasts to adipocytes.[Methods]3T3-L1 preadipocytes were cultured in DMEM high glucose medium containing 10%calf serum.3T3-L1 preadipocytes were induced to differentiate into adipocytes with 0.5 ?M isobutylmethylxanthine,1 ?M dexamethasone and 10 ?g/mL insulin.The oil droplets in the cells were stained with Oil Red O,the content of triglyceride(TG)was measured,and the activity of glycerol-3-phosphate dehydrogenase(GPDH)was measured.The luciferase activity assay and reverse transcription-polymerase chain reaction were used.Reaction(RT-PCR)and Western blot(Western blot)were used to study the inhibitory effect of 2.5-10 ?M CAPE on the differentiation of 3T3-L1 preadipocytes into adipocytes and the regulation of specific lipogenic factors.[Results]CAPE significantly inhibited the accumulation of lipid droplets,significantly reduced the TG content and GPDH activity in a dose-dependent manner,indicating that CAPE effectively inhibited the differentiation of 3T3-L1 preadipocytes into adipocytes,which has potential anti-obesity effects.CAPE concentration-dependent manner significantly reduced mRNA expression of peroxisome proliferator-activated receptor-gamma(PPAR-?)and CCAAT/enhancer-binding protein alpha(C/EBP?)and downstream of PPAR-? and C/EBP? Expression of adipocyte-specific gene fatty acid synthase(FAS),adipocyte-specific fatty acid binding protein 2(aP2),stearoyl-CoA dehydrogenase 1(SCD-1)and lipoprotein(LPL),and after CAPE treatment The transcriptional activity of PPAR-y was significantly decreased,indicating that CAPE inhibits the expression of lipid synthesis transcription factors and downstream factors,thereby inhibiting the differentiation of 3T3-L1 preadipocytes;CAPE treatment significantly up-regulated transforming growth factor-?(TGF?)and Phosphorylation of Smad2 and Smad3,phosphorylation of Smad2 and Smad3 was attenuated in the presence of Alk inhibitors,and levels of PPAR-y and C/EBPa were also restored,suggesting that TGF-?/Smad2,3 signaling is involved in CAPE Causing fat Into suppression.[Conclusion]These results suggest that CAPE might inhibits the lipogenesis of 3T3-L1 adipocytes by regulating PPAR-?,C/EBPa and TGF-? signaling pathways.