Inhibition of aldose reductase ameliorates ethanol-induced steatosis in HepG2 cells

Longxin Qiu, Chengchao Cai, Xiangqian Zhao, Yan Fang, Weibiao Tang, Chang Guo
2017 Molecular Medicine Reports  
Aldose reductase (AR) expression is increased in liver tissue of patients with ethanol-induced liver disease. However, the exact role of AR in the development of ethanol-induced liver disease has yet to be elucidated. The present study aimed to determine the effect of an AR inhibitor on ethanol-induced steatosis in HepG2 cells and to identify possible underlying molecular mechanisms. Steatosis was induced in HepG2 cells by stimulating cells with 100 mM absolute ethanol for 48 h. Oil Red O
more » ... h. Oil Red O staining was used to detect the lipid droplet accumulation in cells. Western blot analyses were used to determine protein expression levels and reverse transcription-quantitative polymerase chain reaction was used to analyze mRNA expression levels. The results showed that AR protein expression was elevated in HepG2 cells stimulated with ethanol. HepG2 cells exhibited marked improvement of ethanol-induced lipid accumulation following treatment with the AR inhibitor zopolrestat. Phosphorylation levels of 5' adenosine monophosphate-activated protein kinase (AMPK) were markedly higher, whereas the mRNA expression levels of sterol-regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) were significantly lower in zopolrestat-treated and ethanol-stimulated HepG2 cells compared with in untreated ethanol-stimulated HepG2 cells. In addition, zopolrestat inhibited the ethanol-induced expression of tumor necrosis factor (TNF)-α. These results suggested that zopolrestat attenuated ethanol-induced steatosis by activating AMPK and subsequently inhibiting the expression of SREBP-1c and FAS, and by suppressing the expression of TNF-α in HepG2 cells.
doi:10.3892/mmr.2017.6313 pmid:28447762 fatcat:qkut5qj255dxzengf6ymnj6cda