Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats

作者：Rui, Bei-bei; Chen, Hao; Jang, Lei; Li, Zhen; Yang, Jing-mo; Xu, Wei-ping^*; Wei, Wei^*

来源：Alcohol and Alcoholism, 2016, 51(1): 11-19.

DOI：10.1093/alcalc/agv126

• ACTIVATED PROTEIN-KINASE
• INDUCED LIVER-DISEASE
• FATTY LIVER
• HEPATOCELLULAR-CARCINOMA
• OXIDATIVE STRESS
• RISK-FACTORS
• INDUCED STEATOSIS
• HEPG2 CELLS
• MECHANISMS
• EXPRESSION

Melatonin is supposed to be an effective hepatoprotective agent. The effects and mechanisms of melatonin on alcoholic fatty liver (AFL) have not been well explored. The aim of this study was to investigate the preventive and therapeutic effects of melatonin on alcohol-induced fatty liver rats. @@@ The AFL rats were induced by intragastric infusion of alcohol plus a high-fat diet for 6 weeks, and melatonin (10, 20, 40 mg/kg) was administered by gastric perfusion. We also established fatty acid overload cell model in HepG2 cells to investigate the effect of melatonin on AMP-activated protein kinase (AMPK) activity. @@@ The results showed that melatonin (20 and 40 mg/kg) administration significantly reduced alcohol-induced hepatic steatosis with lowering activities of serum alanine aminotransferase, aspartate aminotransferase and levels of serum and hepatic triglyceride. The activity of superoxide dismutase was increased and the content of malondialdehyde was decreased in liver homogenates of rats treated with melatonin. Melatonin increased the phosphorylation of AMPK in the liver tissues of alcohol-induced rats as well. Additionally, in vitro studies showed that melatonin increased the expression of melatonin1A receptor (MT1R), whereas luzindole, a receptor antagonist of melatonin, had no effect on its expression. In addition, melatonin reduced the levels of adenosine 3',5'-cyclic monophosphate (cAMP) and increased the phosphorylation of AMPK, and melatonin treatment could markedly reverse these effects. @@@ In conclusion, melatonin could protect against liver injury caused by alcohol gastric perfusion. The effect may be related to alleviating lipid peroxidation and upregulating the activity of AMPK mediated by MT1R signaling pathway.

• 出版日期2016-1
• 单位安徽医科大学