Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Genes (Basel). 2023 Feb 23;14(3):553. doi: 10.3390/genes14030553.
Lipotoxicity is a phenomenon of lipid-induced cellular injury in nonadipose tissue. Excess of free saturated fatty acids (SFAs) contributes to hepatic injury in nonalcoholic fatty liver disease (NAFLD), which has been growing at an unprecedented rate in recent years. SFAs and their derivatives such as ceramides and membrane phospholipids have been shown to induce intrahepatic oxidative damage and ER stress. Autophagy represents a cellular housekeeping mechanism to counter the perturbation in organelle function and activation of stress signals within the cell. Several aspects of autophagy, including lipid droplet assembly, lipophagy, mitophagy, redox signaling and ER-phagy, play a critical role in mounting a strong defense against lipotoxic lipid species within the hepatic cells. This review provides a succinct overview of our current understanding of autophagy-lipotoxicity interaction and its pharmacological and nonpharmacological modulation in treating NAFLD.
脂毒性是指非脂肪组织中脂质诱导的细胞损伤现象。过量的游离饱和脂肪酸（SFAs）导致非酒精性脂肪性肝病（NAFLD）中的肝损伤，近年来该病的发病率呈前所未有的速度增长。SFAs 及其衍生物，如神经酰胺和膜磷脂，已被证明可诱导肝内氧化损伤和内质网应激。自噬代表了一种细胞自我维持机制，可对抗细胞器功能障碍和细胞内应激信号的激活。自噬的几个方面，包括脂滴组装、脂噬、线粒体自噬、氧化还原信号和内质网自噬，在抵御肝细胞内的脂毒性脂质方面发挥着关键作用。本综述简要概述了我们目前对自噬-脂毒性相互作用及其在治疗 NAFLD 中的药理学和非药理学调节的理解。
