非酒精性脂肪性肝病中肝细胞脂肪变性分子机制的研究

Molecular mechanism of hepatocyte steatosis in non-alcoholic fatty liver disease

肝脏在三大营养物质(包括糖、脂肪和蛋白质)的生物转化中起着重要作用。现代社会中多发的肥胖症促进了外周组织中的胰岛素抵抗,并且可能通过诱导肝脏中脂质的积累而引发严重的代谢紊乱,导致非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)。NAFLD可能导致更严重的疾病,如非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)、肝硬化甚至原发性肝癌。NAFLD的特点是肝脏中脂质增加,通常甘油三酯分子代表细胞内和血浆中脂肪酸的主要储存和运输形式,肝脏摄取和自身合成的脂肪酸以富含甘油三酯的极低密度脂蛋白的形式排出肝脏。在营养过剩和肥胖的情况下,肝脂肪酸代谢发生改变,通常导致肝细胞内甘油三酯的积累,并导致NAFLD。肝脏中脂质的累积可以通过增加游离脂肪酸摄入肝脏,减少脂肪酸β氧化或脂质从头合成的发生率增加来追踪。在本文中,我们描述了目前对肝脏中脂肪酸和甘油三酯代谢的理解及其对健康和疾病的调节,提出了未来研究的潜在方向。了解肝脏脂肪积累的分子机制对于NAFLD靶向治疗的发展至关重要。

The liver plays an important role in the biotransformation of 3 major nutrients, including sugar, fat and protein. The increased morbidity of obesity in modern society promotes insulin resistance in human peripheral tissues and may lead to severe metabolic disorders by inducing lipid accumulation in the liver, and cause non-alcoholic fatty liver disease （NAFLD）. NAFLD can lead to non-alcoholic steatohepatitis （NASH）, cirrhosis, even cancer. Triglyceride （TG） is the main form of storage and transport of free fatty acids. Free fatty acids in plasma are ingested and produced in the liver by biosynthesis, and then they are eliminated into plasma in the form of very low density lipoproteins （VLDL）. In the situation of excess nutrition and obesity, changes in the metabolism of free fatty acids lead to the accumulation of TG and NAFLD. The accumulation of lipids in the liver can be traced by increasing the intake of free fattyacids to the liver, reducing the incidence of fatty acid β oxidation or lipid synthesis. In this article, we describe the current research of free fatty acids and TG metabolism in the liver and its regulation mechanism, and the potential direction of future research.