Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
State Key Laboratory of Digestive Diseases, Department of Medicine & Therapeutics and LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
Adv Exp Med Biol. 2018;1061:127-138. doi: 10.1007/978-981-10-8684-7_10.
Non-alcoholic fatty liver disease (NAFLD) will become a dominant cause of hepatocellular carcinoma (HCC) in the coming decade. Whereas the exact molecular mechanisms underlying the progression from simple steatosis, through steatohepatitis, to HCC remains largely unclear, emerging evidence has supported a central role of defective autophagy in the pathogenesis of NAFLD and its complications. Autophagy not only regulates lipid metabolism and insulin resistance, but also protects hepatocytes from injury and cell death. Nevertheless, in inflammation and tumorigenesis, the role of autophagy is more paradoxical. In NAFLD, defective hepatic autophagy occurs at multiple levels through numerous mechanisms and is causally linked to NAFLD-related HCC. In this chapter, we summarize the regulation and function of autophagy in NAFLD and highlight recent identification of potential pharmacological agents for restoring autophagic flux in NAFLD.
非酒精性脂肪性肝病（NAFLD）将在未来十年成为肝细胞癌（HCC）的主要病因。尽管从单纯性脂肪变性，经过脂肪性肝炎，再到 HCC 的进展的确切分子机制在很大程度上仍不清楚，但新出现的证据支持自噬缺陷在 NAFLD 及其并发症发病机制中的核心作用。自噬不仅调节脂质代谢和胰岛素抵抗，还保护肝细胞免受损伤和细胞死亡。然而，在炎症和肿瘤发生中，自噬的作用更加矛盾。在 NAFLD 中，通过多种机制在多个水平发生肝自噬缺陷，并与 NAFLD 相关的 HCC 有因果关系。在本章中，我们总结了自噬在 NAFLD 中的调控和功能，并强调了最近发现的恢复 NAFLD 中自噬流的潜在药物作用机制。
