Resveratrol alleviates alcoholic fatty liver in mice
Resveratrol alleviates alcoholic fatty liver in mice
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DOI：
10.1152/ajpgi.90358.2008
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发表时间：
2008-10-01
影响因子：
4.5
通讯作者：
You, Min
中科院分区：
文献类型：
--
作者：
Ajmo, Joanne M.;Liang, Xiaomei;You, Min
酒精性脂肪肝与沉默调节蛋白 1 (SIRT1) 和 AMP 激活激酶 (AMPK) 的抑制有关，这两种信号分子调节动物肝脏脂质代谢途径。白藜芦醇是一种膳食多酚，已被确定为 SIRT1 和 AMPK 的有效激活剂。在本研究中，我们进行了体内动物实验，测试白藜芦醇逆转长期乙醇喂养对肝脏 SIRT1-AMPK 信号系统的抑制作用并预防酒精性肝脂肪变性发展的能力。白藜芦醇治疗增加了乙醇喂养小鼠肝脏中 SIRT1 的表达水平并刺激了 AMPK 活性。白藜芦醇介导的 SIRT1 和 AMPK 活性增加与甾醇调节元件结合蛋白 1 (SREBP-1) 的抑制和过氧化物酶体增殖物激活受体 γ 共激活剂 α (PGC-1 α) 的激活有关。与此同时，在乙醇喂养的小鼠中，白藜芦醇的施用显着增加了循环脂联素水平并增强了肝脂联素受体 (AdipoR1/R2) 的 mRNA 表达。总之，白藜芦醇治疗导致脂质合成减少，脂肪酸氧化速率增加，并预防酒精性肝脂肪变性。白藜芦醇的保护作用全部或部分是通过上调乙醇喂养小鼠肝脏中 SIRT1-AMPK 信号系统来介导的。我们的研究表明，白藜芦醇可能作为预防或治疗人类酒精性脂肪肝疾病的有前途的药物。
Alcoholic fatty liver is associated with inhibition of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), two critical signaling molecules regulating the pathways of hepatic lipid metabolism in animals. Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK. In the present study, we have carried out in vivo animal experiments that test the ability of resveratrol to reverse the inhibitory effects of chronic ethanol feeding on hepatic SIRT1-AMPK signaling system and to prevent the development of alcoholic liver steatosis. Resveratrol treatment increased SIRT1 expression levels and stimulated AMPK activity in livers of ethanol-fed mice. The resveratrol-mediated increase in activities of SIRT1 and AMPK was associated with suppression of sterol regulatory element binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1 alpha). In parallel, in ethanol-fed mice, resveratrol administration markedly increased circulating adiponectin levels and enhanced mRNA expression of hepatic adiponectin receptors (AdipoR1/R2). In conclusion, resveratrol treatment led to reduced lipid synthesis and increased rates of fatty acid oxidation and prevented alcoholic liver steatosis. The protective action of resveratrol is in whole or in part mediated through the upregulation of a SIRT1-AMPK signaling system in the livers of ethanol-fed mice. Our study suggests that resveratrol may serve as a promising agent for preventing or treating human alcoholic fatty liver disease.