Resveratrol induces autophagy and its interference effect on nonalcoholic steatohepatitis in a murine model

Objective To investigate the effects of resveratrol-induced autophagy on nonalcoholic steatohepatitis induced with methionine- and choline-deficient(MCD) diet in C57BL/6J mice and its potential molecular mechanisms.Methods Forty male C57BL/6J mice were randomized into control group,MCD group,low-dose resveratrol group(100 mg/kg) and high-dose resveratrol group(250 mg/kg )(10 mice in each group);the mice of control group and MCD group were fed with standard or MCD diet,respectively,and the intervention group were fed with MCD diet and given resveratrol by gavage at the same time.After 4 weeks,serum alanine aminotransferase(ALT) level was determined and triglycide(TG) and malondialdehyde(MDA) levels in liver tissue were also determined.The mice were executed to obtain the liver tissue for observing hepatic pathological and lipid changes.The expressions of proteins involved in the autophagic pathways were analyzed with Western blot.Results Compared with those of the control group,the serum ALT(144.17±0.32 U/L)and liver TG(112.77±0.88 mg/g)levels in mice of MCD group increased(P<0.01); the expressions of microtubule-associated protein1 light chain 3(LC3Ⅱ)(1.27±0.01)and adenosine monophosphate-activated protein kinase(AMPK)(1.81±0.09)also increased(P<0.05 for all).Compared with those of the MCD group,the ALT(83.16±0.40 U/L)and the TG(40.75±0.19 mg/g)significantly decreased in the mice of high-dose resveratrol group(P<0.01 for all).Western blot revealed that the expression of LCⅡ(2.25±0.14)and AMPK (3.01±0.16)increased significantly in the mice treated with high-dose resveratrol(P<0.01 for all),but protein kinase B(Akt) and mammalian target of rapamycin(mTOR) expression were not downregulated as expected.Conclusion Resveratrol intervention could attenuate nonalcoholic steatohepatitis in C57BL/6J mice with MCD diet and the effect may be related to the induction of autophagy through activating AMPK signaling pathway.