Lakshman M Raj
Lipid Research Laboratory (151T), VA Medical Center, 50 Irving Street NW, Washington, DC 20422, USA.
Alcohol. 2004 Aug;34(1):45-8. doi: 10.1016/j.alcohol.2004.08.004.
The pathogenesis of alcoholic steatosis is a complex process that is manifested through several mechanisms involving some of or all the following body metabolism components: increased fat synthesis, increased mobilization of depot fat, defective export of fat from the liver, and decreased fat breakdown. Some of the novel findings in these mechanisms involve the down-regulation of peroxisome proliferator-activated receptor alpha and up-regulation of lipogenic enzymes through the induction of sterol regulatory element-binding protein. Yet another mechanism that remains viable is the adenosine 5'-monophosphate-activated protein kinase, which, through a complex mechanism, may regulate the relative concentrations of intracellular malonyl coenzyme A and long-chain acyl-coenzyme A, the key metabolites responsible for the balance between fat synthesis versus degradation pathways. Finally, excess dietary intake of omega-6 polyunsaturated fatty acids may exacerbate alcohol-induced onset of hepatic steatosis and alcoholic liver disease. This may explain why supplementation with lecithin containing omega-6 polyunsaturated fatty acids in a recent clinical trial in human beings failed to show any beneficial effects, although it was partially effective in an animal model. In contrast, dietary intake of omega-3 polyunsaturated fatty acids in moderation may have a protective effect against steatosis and alcoholic liver disease.
酒精性脂肪变性的发病机制是一个复杂的过程，通过涉及以下部分或全部身体代谢成分的多种机制表现出来：脂肪合成增加、储存脂肪动员增加、肝脏脂肪输出缺陷以及脂肪分解减少。这些机制中的一些新发现包括过氧化物酶体增殖物激活受体α的下调以及通过固醇调节元件结合蛋白的诱导导致生脂酶上调。另一种仍然可行的机制是5'-单磷酸腺苷激活蛋白激酶，它通过复杂的机制可能调节细胞内丙二酰辅酶A和长链酰基辅酶A的相对浓度，这两种关键代谢物负责脂肪合成与降解途径之间的平衡。最后，过量摄入ω-6多不饱和脂肪酸可能会加剧酒精诱导的肝脂肪变性和酒精性肝病的发生。这或许可以解释为什么在最近一项针对人类的临床试验中，补充含有ω-6多不饱和脂肪酸的卵磷脂未能显示出任何有益效果，尽管它在动物模型中部分有效。相比之下，适度摄入ω-3多不饱和脂肪酸的饮食可能对脂肪变性和酒精性肝病具有保护作用。
