Fish oil fed prior to ethanol administration prevents acute ethanol-induced fatty liver in mice

Background/Aims We examined whether dietary fish oil can prevent acute ethanol (alcohol)-induced fatty liver. Methods Mice were fed safflower oil, fish oil, or safflower oil plus a PPARα activator on the day prior to ethanol administration. Oil red O staining, serum analysis, and RT-PCR were used to analyze ethanol-induced fatty liver. Results In mice fed safflower oil, ethanol increased liver TG 3-fold, with activation of SREBP-1c and ChREBP, which promote de novo lipogenesis, and increases in expression of mRNAs for PPARγ and DGATs mRNAs, which promote TG synthesis. When mice were fed fish oil, ethanol-induced fatty liver was reduced by 73%. Fish oil decreased SREBP-1c activity and increased PPARα activity. However, levels of DGAT1, DGAT2, ChREBP, LPK, and PPARγ mRNAs were increased in response to ethanol in mice fed fish oil. Prior administration of Wy14643, PPARα activator, did not inhibit ethanol-induced fatty liver, suggesting that PPARα played little role in prevention of ethanol-induced fatty liver by fish oil. Conclusions A single dose of ethanol increases the liver TG level via several mechanisms; however, prior ingestion of fish oil effectively prevents ethanol-induced fatty liver, at least in part, by decreasing basal SREBP-1c activity, especially a marked reduction in SCD1.