title: Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Anhui No. 2 Province People's Hospital, Hefei, Anhui 200041, China.
authors.forename: Bei-bei
authors.initials: BB
authors.lastname: Rui
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Anhui No. 2 Province People's Hospital, Hefei, Anhui 200041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jang
authors.affiliation: Anhui No. 2 Province People's Hospital, Hefei, Anhui 200041, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Anhui Provincial Cancer Hospital, Hefei, Anhui 230001, China.
authors.forename: Jing-mo
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Anhui Medical University affiliated Provincial Hospital, Hefei, Anhui 230001, China xu_weiping666@163.com wwei@ahmu.edu.cn.
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China xu_weiping666@163.com wwei@ahmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D044122:Receptor, Melatonin, MT1; D014280:Triglycerides; D014363:Tryptamines; C057154:luzindole; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D055372:AMP-Activated Protein Kinases; D008550:Melatonin