脂肪酸代谢异常促进非酒精性脂肪肝发生发展的分子机制研究进展

Molecular Mechanisms of Fatty Acid Metabolism Abnormalities Promotes Non-alcoholic Fatty Liver Disease

非酒精性脂肪肝(NAFLD)是一种脂肪在肝脏中积累的慢性肝病,并伴有肥胖和胰岛素抵抗等形式的代谢功能障碍,已成为我国最常见的肝脏疾病。肝脏的脂肪酸代谢是由脂肪酸的摄取和输出,脂肪酸从头合成和脂肪酸β-氧化利用共同调节的。本文综述了NAFLD肝脏脂肪酸异常代谢的分子机制,重点介绍了肝脏脂质稳态失衡的几条主要途径。在NAFLD,脂肪酸获取和消耗的平衡被打破,肝脂肪酸摄取和脂肪酸从头合成增加,线粒体功能受损,过氧化物酶体和细胞色素脂肪酸氧化增加,VLDL输出增加,而补偿性增强的脂肪酸氧化与输出不足以使脂肪酸水平恢复正常,肝脏脂肪酸积累开始。肝细胞内脂肪酸稳态的失调致有毒脂质产生,进一步诱发氧化应激和脂毒性,促进细胞器功能损伤、细胞凋亡和疾病进展。

Nonalcoholic fatty liver disease(NAFLD),a chronic liver disease in which fat accumulates in the liver and is associated with metabolic dysfunction in the form of obesity and insulin resistance,has become the most common liver disease in China.Fatty acid metabolism in the liver is regulated by a combination of fatty acid uptake and output,de novo lipogenesis and fatty acidβ-oxidation.This article reviews the molecular mechanisms underlying abnormal hepatic fatty acid metabolism in NAFLD,focusing on several major pathways of hepatic lipid homeostasis imbalance.In NAFLD,the balance of fatty acid acquisition and depletion is disrupted,hepatic fatty acid uptake and fatty acid synthesis from scratch are increased,mitochondrial function is impaired,peroxisomal and cytochrome fatty acid oxidation is increased,VLDL output is increased,and compensatory enhancement of fatty acid oxidation and output is insufficient to return fatty acid levels to normal,and hepatic fatty acid accumulation begins.Dysregulation of fatty acid homeostasis in hepatocytes results in the production of toxic lipids,which further induces oxidative stress and lipotoxicity to promote organelle dysfunction,apoptosis and disease progression.