Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan.
School of Medicine, National Yang Ming Chiao Tung University, Taipei City 112, Taiwan.
Int J Mol Sci. 2022 Sep 2;23(17):10055. doi: 10.3390/ijms231710055.
Metabolic associated fatty liver disease (MAFLD) is one of the most common causes of chronic liver disease worldwide. To date, there is no FDA-approved treatment, so there is an urgent need to determine its pathophysiology and underlying molecular mechanisms. Autophagy is a lysosomal degradation pathway that removes damaged organelles and misfolded proteins after cell injury through endoplasmic reticulum stress or starvation, which inhibits apoptosis and promotes cell survival. Recent studies have shown that autophagy plays an important role in removing lipid droplets from hepatocytes. Autophagy has also been reported to inhibit the production of pro-inflammatory cytokines and provide energy for the hepatic stellate cells activation during liver fibrosis. Thyroid hormone, irisin, melatonin, hydrogen sulfide, sulforaphane, DA-1241, vacuole membrane protein 1, nuclear factor erythroid 2-related factor 2, sodium-glucose co-transporter type-2 inhibitors, immunity-related GTPase M, and autophagy-related gene 7 have been reported to ameliorate MAFLD via autophagic induction. Lipid receptor CD36, SARS-CoV-2 Spike protein and leucine aminopeptidase 3 play a negative role in the autophagic function. This review summarizes recent advances in the role of autophagy in MAFLD. Autophagy modulates major pathological changes, including hepatic lipid metabolism, inflammation, and fibrosis, suggesting the potential of modulating autophagy for the treatment of MAFLD.
代谢相关性脂肪性肝病（MAFLD）是全球最常见的慢性肝病病因之一。迄今为止，尚无获得美国食品和药物管理局（FDA）批准的治疗方法，因此迫切需要确定其病理生理学和潜在的分子机制。自噬是一种溶酶体降解途径，可在细胞损伤后通过内质网应激或饥饿清除受损的细胞器和错误折叠的蛋白质，从而抑制细胞凋亡并促进细胞存活。最近的研究表明，自噬在从肝细胞中清除脂滴方面起着重要作用。自噬还被报道可抑制促炎细胞因子的产生，并在肝纤维化过程中为肝星状细胞激活提供能量。甲状腺激素、鸢尾素、褪黑素、硫化氢、萝卜硫素、DA-1241、液泡膜蛋白 1、红细胞生成素相关因子 2、钠-葡萄糖共转运蛋白 2 抑制剂、免疫相关 GTP 酶 M 和自噬相关基因 7 已被报道可通过诱导自噬来改善 MAFLD。脂质受体 CD36、SARS-CoV-2 Spike 蛋白和亮氨酸氨肽酶 3 在自噬功能中起负向作用。本综述总结了自噬在 MAFLD 中的作用的最新进展。自噬调节主要的病理变化，包括肝脂质代谢、炎症和纤维化，提示调节自噬可能成为治疗 MAFLD 的一种方法。
