Donohue Terrence M
Liver Study Unit, Research Service (151), VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, USA.
World J Gastroenterol. 2007 Oct 7;13(37):4974-8. doi: 10.3748/wjg.v13.i37.4974.
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.
酒精性脂肪肝（脂肪变性）被认为是乙醇代谢过程中还原当量过度生成所致，从而加剧脂肪堆积。最近的研究结果揭示了一幅更为复杂的图景，其中乙醇氧化仍然是必需的，但特定的转录以及体液因子也起着重要作用。涉及的转录因子包括固醇调节元件结合蛋白1（SREBP-1），其被激活以诱导调节脂质生物合成的基因。相反，乙醇摄入会导致脂质（脂肪酸）氧化普遍下调，这反映了过氧化物酶体增殖物激活受体α（PPAR-α）的失活，PPAR-α调节参与脂肪酸氧化的基因。第三个转录因子是早期生长反应因子1（Egr-1），它在脂肪变性发作之前被强烈诱导。所有这些因子的活性都受主要调节酶AMP激酶的活性控制。重要的体液因子，包括脂联素和肿瘤坏死因子-α（TNF-α），也调节酒精性脂肪变性。它们的水平受酒精摄入以及彼此的影响。本综述将总结这些蛋白质在乙醇诱发的脂肪肝中的作用。由于脂肪变性现在被视为晚期肝脏病变的重要危险因素，因此了解其病因中的分子机制对于开发有效的治疗方法至关重要。
