Molecular mechanism of alcoholic fatty liver.
Molecular mechanism of alcoholic fatty liver.
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DOI：
10.4103/0253-7613.96297
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发表时间：
2012-05
影响因子：
2.4
通讯作者：
Casey CA
中科院分区：
文献类型：
--
作者：
Rasineni K;Casey CA
酒精滥用和长期酒精消费仍然是一个主要的公共卫生问题，是导致高发病率的原因。酒精性脂肪肝一般始于肝脏脂肪变性，如果病因持续存在，必然会发展为脂肪性肝炎和肝硬变。酒精性脂肪肝最初的生化解释集中在酒精代谢改变肝脏氧化还原状态和抑制脂肪酸氧化的能力上。随后的研究发现，抑制脂肪酸氧化和诱导脂肪生成可以在酒精条件下发生。乙醇激活了固醇调节元件结合蛋白1，诱导了一系列产脂酶。这些作用可能部分归因于抑制AMP依赖的蛋白激酶，降低血浆脂联素或增加肝脏中肿瘤坏死因子-α的水平。它们反过来激活脂肪生成途径，抑制脂肪酸氧化。除了脂肪酸的合成和氧化，乙醇还改变了肝细胞的脂滴(LD，甘油三酯的储存形式，TG)代谢和肝脏极低密度脂蛋白(VLDL)的分泌。由于脂肪变性现在被认为是晚期肝脏病理的一个重要危险因素，了解其病因的分子机制为逆转酒精性脂肪肝提供了新的治疗靶点。
Ethanol abuse and chronic ethanol consumption remains a major public health problem and is responsible for a high rate of morbidity. Alcohol-induced fatty liver generally begins as hepatic steatosis, and if the cause persists, this invariably progresses to steatohepatitis and cirrhosis. The original biochemical explanation for an alcoholic fatty liver centered on the ability of ethanol metabolism to shift the redox state of the liver and inhibit fatty acid oxidation. Subsequent studies found repression of fatty acid oxidation and that the induction of lipogenesis can occur in alcoholic conditions. Ethanol activates sterol regulatory element binding protein 1, inducing a battery of lipogenic enzymes. These effects may be due in part to inhibition of AMP-dependent protein kinase, reduction in plasma adiponectin or increased levels of TNF-α the liver. They in turn activate lipogenic pathways and inhibit fatty acid oxidation. Besides the fatty acid synthesis and oxidation, ethanol also alters lipid droplet (LD, the storage form of triglycerides, TG) metabolism in hepatocytes and very low-density lipoprotein (VLDL) secretion from liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology provides new therapeutic targets to reverse the alcoholic fatty liver.
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影响因子：
4.1
作者：
Lee, GY;Kim, NH;Kim, YS
通讯作者：
Kim, YS
影响因子：
15.9
作者：
García-Ruiz, C;Colell, A;Fernández-Checa, JC
通讯作者：
Fernández-Checa, JC
DOI：
10.1073/pnas.96.20.11041
发表时间：
1999-09-28
影响因子：
11.1
作者：
Brown, MS;Goldstein, JL
通讯作者：
Goldstein, JL
影响因子：
2.3
作者：
Crabb, DW;Galli, A;You, M
通讯作者：
You, M
影响因子：
4.3
作者：
Kharbanda, Kusum K.;Todero, Sandra L.;Tuma, Dean J.
通讯作者：
Tuma, Dean J.