Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice
Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice
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DOI：
10.1152/ajpgi.00456.2009
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发表时间：
2010-03-01
影响因子：
4.5
通讯作者：
You, Min
中科院分区：
文献类型：
--
作者：
Shen, Zheng;Liang, Xiaomei;You, Min
沈正，梁旭，罗杰斯，D，游明。脂联素-SIRT1-AMPK信号转导通路在罗格列酮抗小鼠酒精性脂肪肝中的作用。Am J Physiol胃肠病肝生理学298：G364-G374,2010。2009年12月10日首次出版；DOI：10.1152/ajpgi.00456.2009。-酒精性脂肪肝的发生与动物体内脂肪细胞来源的脂联素水平降低、肝脂联素受体减少和肝脂联素信号紊乱有关。过氧化体增殖物激活受体-γ(PPAR-γ)在脂肪组织脂联素的调节中起关键作用。本研究的目的是测试已知的PPAR-γ激动剂罗格列酮逆转乙醇对脂联素表达及其肝脏信号转导的抑制作用，并减轻酒精性肝脂肪变性的能力。小鼠饲喂改良的Lieber-DeCarli乙醇液体饲料4wk，或配对喂养对照饲料。在喂养研究的最后2周，四组小鼠分别给予3或10 mg·kg-1体重的罗格列酮，并在饮食中加入或不加入乙醇。罗格列酮和乙醇合用可增加小鼠肝组织脂联素的表达和循环水平，增强肝脂联素受体的表达。这些增加与肝脏sirtuin 1(SIRT1)-AMP激活激酶(AMPK)信号系统的激活密切相关。与受刺激的SIRT1-AMPK信号相一致，罗格列酮可增强脂肪酸氧化酶的表达，使脂类1的表达正常化，并阻止脂肪酶编码基因的表达上调，从而导致乙醇喂养小鼠肝脏脂肪酸氧化增加，脂肪生成减少，脂肪变性减轻。肝脏脂联素-SIRT1-AMPK信号的增强至少部分参与了罗格列酮对小鼠酒精性脂肪肝的保护作用。
Shen Z, Liang X, Rogers CQ, Rideout D, You M. Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol 298: G364-G374, 2010. First published December 10, 2009; doi: 10.1152/ajpgi.00456.2009.-The development of alcoholic fatty liver is associated with reduced adipocyte-derived adiponectin levels, decreased hepatic adiponectin receptors, and deranged hepatic adiponectin signaling in animals. Peroxisomal proliferator-activated receptor-gamma (PPAR-gamma) plays a key role in the regulation of adiponectin in adipose tissue. The aim of the present study was to test the ability of rosiglitazone, a known PPAR-gamma agonist, to reverse the inhibitory effects of ethanol on adiponectin expression and its hepatic signaling, and to attenuate alcoholic liver steatosis in mice. Mice were fed modified Lieber-DeCarli ethanol-containing liquid diets for 4 wk or pair-fed control diets. Four groups of mice were given a dose of either 3 or 10 mg.kg body wt(-1).day(-1) of rosiglitazone with or without ethanol in their diets for the last 2 wk of the feeding study. Coadministration of rosiglitazone and ethanol increased the expression and circulating levels of adiponectin and enhanced the expression of hepatic adiponectin receptors (AdipoRs) in mice. These increases correlated closely with the activation of a hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK) signaling system. In concordance with stimulated SIRT1-AMPK signaling, rosiglitazone administration enhanced expression of fatty acid oxidation enzymes, normalized lipin 1 expression, and blocked elevated expression of genes encoding lipogenic enzymes which, in turn, led to increased fatty acid oxidation, reduced lipogenesis, and alleviation of steatosis in the livers of ethanol-fed mice. Enhanced hepatic adiponectin-SIRT1-AMPK signaling contributes, at least in part, to the protective action of rosiglitazone against alcoholic fatty liver in mice.