Molecular mechanisms of alcoholic fatty liver.
Molecular mechanisms of alcoholic fatty liver.
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DOI：
10.1111/j.1530-0277.2008.00827.x
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Song, Byoung-Joon
中科院分区：
文献类型：
--
作者：
Purohit, Vishnudutt;Gao, Bin;Song, Byoung-Joon
关键词：
酒精性脂肪肝是一种潜在的病理状态，如果继续饮酒，可以进展为脂肪性肝炎，纤维化和肝硬化。酒精暴露可通过增加NADH/NAD+比值、增加固醇调节元件结合蛋白-1（SREBP-1）活性、降低过氧化物酶体增殖物激活受体-α（PPAR-α）活性和增加肝脏补体C3水平诱导脂肪肝。酒精可通过降低AMP活化蛋白激酶和sirtuin-1的活性来增加SREBP-1的活性。酒精暴露后产生的肿瘤坏死因子-α（TNF-α）可能通过上调SREBP-1活性导致脂肪肝，而甜菜碱和吡格列酮可能通过下调SREBP-1活性减轻脂肪肝。PPAR-α激动剂具有减轻酒精性脂肪肝的潜力。脂联素和白细胞介素-6可能通过上调PPAR-α和胰岛素信号通路，下调SREBP-1活性，抑制TNF-α的产生而减轻酒精性脂肪肝。最近的研究表明，肝星状细胞来源的内源性大麻素旁分泌激活肝大麻素受体1也有助于酒精性脂肪肝的发展。此外，参与脂肪酸的线粒体和/或过氧化物酶体β-氧化的酶的氧化修饰和失活可能有助于肝脏中的脂肪蓄积。
Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element-binding protein-1 (SREBP-1) activity, decreasing peroxisome proliferator-activated receptor-α (PPAR-α) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP-1 activity by decreasing the activities of AMP-activated protein kinase and sirtuin-1. Tumor necrosis factor-α (TNF-α) produced in response to alcohol exposure may cause fatty liver by up-regulating SREBP-1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down-regulating SREBP-1 activity. PPAR-α agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin-6 may attenuate alcoholic fatty liver by up-regulating PPAR-α and insulin signaling pathways while down-regulating SREBP-1 activity, and suppressing TNF-α production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell-derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal β-oxidation of fatty acids could contribute to fat accumulation in the liver.
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影响因子：
4.4
作者：
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