Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats
Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats
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DOI：
10.1093/alcalc/agv126
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发表时间：
2016-01-01
影响因子：
2.8
通讯作者：
Wei, Wei
中科院分区：
文献类型：
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作者：
Rui, Bei-bei;Chen, Hao;Wei, Wei
褪黑素被认为是一种有效的肝脏保护剂。褪黑素对酒精性脂肪肝（AFL）的影响及其机制尚未得到很好的探讨。本研究旨在探讨褪黑素对酒精性脂肪肝大鼠的防治作用。采用酒精灌胃加高脂饮食诱导AFL大鼠6周，胃灌注褪黑素（10、20、40 mg/kg）。我们还在HepG2细胞中建立脂肪酸过载细胞模型，研究褪黑素对amp活化蛋白激酶（AMPK）活性的影响。结果表明，褪黑素（20和40 mg/kg）可降低血清丙氨酸转氨酶、天冬氨酸转氨酶活性以及血清和肝脏甘油三酯水平，显著降低酒精性肝脂肪变性。褪黑素使大鼠肝脏匀浆中超氧化物歧化酶活性升高，丙二醛含量降低。褪黑素也增加了酒精诱导的大鼠肝组织中AMPK的磷酸化。此外，体外研究表明，褪黑素增加褪黑素1a受体（MT1R）的表达，而褪黑素受体拮抗剂卢吲哚对其表达没有影响。此外，褪黑激素降低了腺苷3′，5′-环单磷酸腺苷（cAMP）的水平，增加了AMPK的磷酸化，褪黑激素治疗可以显著逆转这些作用。由此可见，褪黑素对酒精胃灌流所致肝损伤具有保护作用。其作用可能与MT1R信号通路介导的减轻脂质过氧化和上调AMPK活性有关。
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.