肝细胞甘油三酯代谢途径异常与脂肪肝

脂肪肝(NAFLD)既可是一个独立的疾病，也可是一类疾病的伴发疾病，肥胖患者、脂肪营养不良症患者、糖尿病患者均伴发脂肪肝。脂肪肝时肝细胞内蓄积的脂质多为甘油三酯，因此肝细胞甘油三酯代谢紊乱是脂肪肝发生最主要原因。肝细胞甘油三酯蓄积会破坏其对胰岛素敏感性，促进肝糖异生导致高血糖，也可引起肝细胞极低密度脂蛋白分泌增加，升高血脂。本文详细阐述肝细胞甘油三酯代谢途径的重要步骤，探讨这些步骤异常与脂肪肝之间的关系，为脂肪肝药物设计提供新靶点。的每条通路的各个步骤，探讨这些步骤异常与脂肪肝之间的关系，为脂肪肝药物设计提供新靶点。

Anomaly of Triglyceride Metabolism in Liver Lead to NAFLD

Non-alcoholic fatty liver disease (NAFLD) is an independent or concomitant metabolic disease associated to obesity, lipodystrophy and diabetes. NAFLD is characterized by accumulation of triglyceride in hepatocytes. Factors influencing metabolisms of triglyceride in liver can be involved for inducing NAFLD. There are two sources of liver fatty acid, one is from fatty acid uptake from circulation, and the other is from fatty acid de novo synthesis. Under physiological conditions, fatty acid uptake plays a leading role in triglyceride production. But in NAFLD, fatty acid de novo synthesis is more important for triglyceride accumulation. Fatty acid can enter mitochondria for β-oxidation and generate ketone bodies, which can be uptaken by myocardium, brain and skeletal muscle. Triglyceride produced by fatty acid esterification will be packaged into VLDL and secrete to plasma. Factors affect these four pathways will disturb the homeostasis of triglyceride metabolism, causing accumulation anomaly. The triglyceride accumulation in liver can damage insulin sensibility, stimulate gluconeogenesis, and induce hyperglycemia. Triglyceride accumulated in hepatocytes will accelerate VLDL packaging and secretion, then lead to hyperglyceridemia. This review focused on pathways of triglyceride metabolism in the context of available drug targets for NAFLD treatments.