ABSTRACT
Objective To investigate the effects of high fat diet on hepatic autophagy in mice and analyze the possi-ble 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 detected .The expression of hepatic AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) protein and autophagic markers including LC3Ⅱ, P 62 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 was up-regulated mildly in HFD fed mice at 8 weeks(P<0.05), but the change dramatically was reversed , hepatic LC3Ⅱ was significantly lower in HFD fed mice at 12,16 weeks, as well as P62 was increased in HFD fed animals (all P<0.05).HFD suppressed phos-phorylation 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 is in dynamic change in high-fat diet mice , long term high-fat diet severely suppressed hepatic autophagy , which is associated with decreased p-AMPK and increased p-mTOR.