Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany.
Centre for Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany.
Prog Lipid Res. 2014 Apr;54:86-112. doi: 10.1016/j.plipres.2014.02.002. Epub 2014 Mar 6.
Triacyglycerols are a major energy reserve of the body and are normally stored in adipose tissue as lipid droplets (LDs). The liver, however, stores energy as glycogen and digested triglycerides in the form of fatty acids. In stressed condition such as obesity, imbalanced nutrition and drug induced liver injury hepatocytes accumulate excess lipids in the form of LDs whose prolonged storage leads to disease conditions most notably non-alcoholic fatty liver disease (NAFLD). Fatty liver disease has become a major health burden with more than 90% of obese, nearly 70% of overweight and about 25% of normal weight patients being affected. Notably, research in recent years has shown LD as highly dynamic organelles for maintaining lipid homeostasis through fat storage, protein sorting and other molecular events studied in adipocytes and other cells of living organisms. This review focuses on the molecular events of LD formation in hepatocytes and the importance of cross talk between different cell types and their signalling in NAFLD as to provide a perspective on molecular mechanisms as well as possibilities for different therapeutic intervention strategies.
甘油三酯是人体的主要能量储备物质,通常以脂滴(LDs)的形式储存在脂肪组织中。然而,肝脏以糖原的形式储存能量,并以脂肪酸的形式储存消化的甘油三酯。在肥胖、营养失衡和药物性肝损伤等应激状态下,肝细胞会以 LD 的形式积累过量的脂肪,其长期储存会导致疾病,最显著的是非酒精性脂肪性肝病(NAFLD)。脂肪肝疾病已成为一个主要的健康负担,超过 90%的肥胖患者、近 70%的超重患者和约 25%的正常体重患者受到影响。值得注意的是,近年来的研究表明,LD 是通过脂肪储存、蛋白质分拣和其他在脂肪细胞和其他生物体细胞中研究的分子事件来维持脂质平衡的高度动态细胞器。本综述重点介绍了肝细胞中 LD 形成的分子事件,以及不同细胞类型之间的串扰及其在 NAFLD 中的信号转导的重要性,以期提供对分子机制以及不同治疗干预策略的可能性的观点。