Ikura Yoshihiro, Caldwell Stephen H
Department of Pathology, Takatsuki General Hospital 1-3-13, Kosobecho, Takatsuki 569-1192, Japan.
Division of Gastroenterology and Hepatology, University of Virginia Charlottesville, Virginia 22908-0708, USA.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):8699-708. eCollection 2015.
Steatosis is a characteristic morphological change of alcoholic liver disease, but its pathologic significance is still obscure. Regardless of cell types, intracellular lipid droplets are coated with a phospholipid monolayer, on which many kinds of lipid droplet-associated proteins are present. These proteins, such as the perilipin family of proteins and the cell death inducing DNA fragmentation factor (DFF) 45-like effectors, are recognized to play important roles in lipid metabolism in the physiological settings. In addition, recent lipidology studies have revealed that expression of the lipid droplet-associated proteins possibly participate in the pathologic processes of many metabolic disorders, including fatty liver and insulin resistance. Hence, controlling protein expressions is expected to offer novel therapeutic options. In this review, we summarize collected data concerning the potential contribution of the lipid droplet-associated proteins to the development of alcoholic fatty liver. Without exception, existing data indicates that the lipid droplet-associated proteins, especially the perilipin family proteins, are important factors in alcoholic fatty liver. These proteins exert a prosteatotic effect, and their expression is closely associated with lipotoxicity based on endoplasmic reticulum stress and oxidative injury. Although suppression of their expression may be beneficial, careful consideration is required because these proteins simultaneously function as protective factors against lipotoxicity.
脂肪变性是酒精性肝病的特征性形态学改变，但其病理意义仍不明确。无论细胞类型如何，细胞内脂质滴都被磷脂单分子层包裹，上面存在多种与脂质滴相关的蛋白质。这些蛋白质，如脂联素家族蛋白和细胞死亡诱导DNA片段化因子（DFF）45样效应物，在生理环境下的脂质代谢中发挥重要作用。此外，最近的脂质学研究表明，与脂质滴相关的蛋白质的表达可能参与包括脂肪肝和胰岛素抵抗在内的许多代谢紊乱的病理过程。因此，控制蛋白质表达有望提供新的治疗选择。在这篇综述中，我们总结了关于与脂质滴相关的蛋白质对酒精性脂肪肝发展的潜在贡献的收集数据。毫无例外，现有数据表明，与脂质滴相关的蛋白质，尤其是脂联素家族蛋白，是酒精性脂肪肝的重要因素。这些蛋白质发挥促脂肪变性作用，其表达与基于内质网应激和氧化损伤的脂毒性密切相关。虽然抑制它们的表达可能有益，但由于这些蛋白质同时作为抗脂毒性的保护因子发挥作用，所以需要谨慎考虑。
