Resveratrol ameliorates hepatic steatosis and inflammation in methionine/choline-deficient diet-induced steatohepatitis through regulating autophagy.
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease that can progress to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Resveratrol, a naturally occurring phytoalexin, is believed to have therapeutic effects on hepatic steatosis. However, the effect of resveratrol on NASH and the underlying mechanism is not fully illustrated. In the present study, we aimed to exam the effect of resveratrol on methionine/choline-deficient (MCD) diet or medium-induced hepatic steatosis, oxidation and inflammation, and to explore the possible mechanism.


METHODS
C57BL/6 mice and AML12 cells were treated with MCD alone or in combination with different concentrations of resveratrol (100 mg/kg/day or 250 mg/kg/day for mice and 25 μmol/L, 50 μmol/L, or 100 μmol/L for cells). Levels of aminotransferases (ALT), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) were measured, concentrations of triglyceride (TG) and thiobarbituric acid reactive substances (TBARs) were determined, and expressions of proteins involved in autophagy were analyzed.


RESULTS
The results indicate that MCD diet or medium induced NASH in mouse and AML12 cell, which was confirmed by the elevated levels of TG, TNF-α, IL-1β, IL-6, ALT and TBARS in mice serum or cell culture medium. Resveratrol administration slowed down NASH progression, decreased the levels of ALT, TG, TBARS, IL-1β, IL-6, downregulated mRNA expressions of TNF-α, IL-1β, IL-6, and regulated the expressions of proteins involved in autophagy, both in vitro and in vivo. However, an autophagical inhibitor significantly impaired the protective role of resveratrol on liver injury and inflammation.


CONCLUSIONS
Resveratrol can attenuate hepatic steatosis and inflammation in MCD-induced NASH by regulating autophagy. Thus, resveratrol may be a promising agent for inhibiting lipid accumulation and inflammatory processes associated with NASH.
Guangdong Provincial Institute of Public Health, Guangdong Provincial Centre for Disease Control and Prevention, Guangzhou, 511430, China. jiguiyuan@126.com.
Guiyuan
G
Ji
Guangdong Provincial Institute of Public Health, Guangdong Provincial Centre for Disease Control and Prevention, Guangzhou, 511430, China. wangyuqi0315@126.com.|Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. wangyuqi0315@126.com.
Yuqi
Y
Wang
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. axmydbx@163.com.
Yingxun
Y
Deng
Institute of Toxicology, Guangdong Provincial Centre for Disease Control and Prevention, Guangzhou, 511430, China. lixinsm@aliyun.com.
Xin
X
Li
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. zhuoqingjiang@sina.com.
Zhuoqin
Z
Jiang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects*; D002796:Choline Deficiency / Q000150:complications; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D008297:Male; D008715:Methionine / Q000172:deficiency; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D013267:Stilbenes; D008715:Methionine; D000077185:Resveratrol