Alcohol-induced steatosis in liver cells.
Alcohol-induced steatosis in liver cells.
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DOI：
10.3748/wjg.v13.i37.4974
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发表时间：
2007-10
影响因子：
4.3
通讯作者：
T. Donohue
中科院分区：
文献类型：
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作者：
T. Donohue
酒精性脂肪肝（脂肪变性）被认为是由于乙醇代谢产生过多的还原性等效物，从而促进脂肪积累。最近的发现揭示了一个更复杂的情况，乙醇氧化仍然是必需的，但特定的转录和体液因素也有重要的作用。涉及的转录因子包括甾醇调节元件结合蛋白1 (SREBP-1)，它被激活以诱导调节脂质生物合成的基因。相反，乙醇消耗导致脂质（脂肪酸）氧化的普遍下调，这反映了调节脂肪酸氧化相关基因的过氧化物酶体增殖物活化受体α (ppar - α)失活。第三个转录因子是早期生长反应-1 (Egr-1)，它在脂肪变性发病前被强烈诱导。所有这些因子的活性都受主要调节酶AMP激酶的活性支配。重要的体液因子，包括脂联素和肿瘤坏死因子α (tnf - α)，也调节酒精诱导的脂肪变性。它们的水平受到酒精摄入量和彼此的影响。本文就这些蛋白在乙醇性脂肪肝中的作用作一综述。由于脂肪变性现在被认为是晚期肝脏病理的重要危险因素，因此了解其病因的分子机制对于开发有效的治疗方法至关重要。
Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required, but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1) which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-alpha (TNF-alpha), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.