Function of Autophagy in Nonalcoholic Fatty Liver Disease.
Function of Autophagy in Nonalcoholic Fatty Liver Disease.
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DOI：
10.1007/s10620-015-4025-x
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Czaja MJ
中科院分区：
文献类型：
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作者：
Czaja MJ
自噬是一种溶酶体降解途径，其功能是通过在应激时提供能量或在损伤后清除受损的细胞器和蛋白质来促进细胞存活。自噬参与非酒精性脂肪性肝病（NAFLD）的发病机制，这一发现首次提出，该途径介导肝细胞内脂质的分解，因此可能调节肝脂肪变性的发生。随后的研究表明，自噬在肝细胞和其他肝细胞类型（如巨噬细胞和星状细胞）中具有其他关键功能，可调节胰岛素敏感性、肝细胞损伤、先天免疫、纤维化和癌变。这些发现提示了自噬在NALD的发展和发展为NASH及其并发症中的一些可能的机制作用。自噬在肝脏中的功能，以及与肥胖和衰老等易患NAFLD的条件相关的肝自噬减少的发现，表明自噬可能是该疾病的一个新的治疗靶点。
Autophagy is a lysosomal degradative pathway that functions to promote cell survival by supplying energy in times of stress or by removing damaged organelles and proteins after injury. The involvement of autophagy in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) was first suggested by the finding that this pathway mediates the breakdown of intracellular lipids in hepatocytes and therefore may regulate the development of hepatic steatosis. Subsequent studies have demonstrated additional critical functions for autophagy in hepatocytes and other hepatic cell types such as macrophages and stellate cells that regulate insulin sensitivity, hepatocellular injury, innate immunity, fibrosis and carcinogenesis. These findings suggest a number of possible mechanistic roles for autophagy in the development of NALD and progression to NASH and its complications. The functions of autophagy in the liver, together with findings of decreased hepatic autophagy in association with conditions that predispose to NAFLD such as obesity and aging, suggest that autophagy may be a novel therapeutic target in this disease.