Abstract: Objective To investigate the effects of high fat diet on hepatic autophagy in mice and analyze the possible mechanism. Methods C57BL male mice were fed with either normal diet or high-fat diet (HFD) for 8 ,12 or 16 weeks.The mice were sacrificed after measuring the body weight. The mesentery and epididymal fat tissue weight，the liver weight and the hepatic lipid accumulation were tested. The expression of hepatic AMP-activated protein kinase （AMPK） and mammalian target of rapamycin （mTOR） protein and autophagic markers including LC3Ⅱ, P62 protein were measured by western blot. Results HFD-fed mice displayed significantly heavier body weight at 16 weeks and significantly heavier intra abdominal fat weight and lipid overaccumulation in liver at 8,12,16weeks(all P<0.01）. Western blot showed hepatic LC3Ⅱexpression were up-regulated mildly in HFD fed mice at 8 weeks（P<0.05）, but the change dramatically was reversed, hepatic LC3-II were significantly lower in HFD fed mice at 12,16weeks, as well as P62 were increased in HFD fed animals(all P<0.05）. HFD suppressed phosphorylation of AMPK and increased phosphorylation of mTOR levels in liver at 8,12,16 weeks, compared to the normal-diet fed mice. Conclusions Our data demonstrate that hepatic autophagy was in dynamic change in high-fat diet mice, long term high-fat diet severely suppressed hepatic autophagy, which was associated with decreased p- AMPK and increased p-mTOR.

Key words: autophagy, hepatic cell, high fat diet