Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide and is strongly associated with the presence of oxidative stress. Disturbances in lipid metabolism lead to hepatic lipid accumulation, which affects different reactive oxygen species (ROS) generators, including mitochondria, endoplasmic reticulum, and NADPH oxidase. Mitochondrial function adapts to NAFLD mainly through the downregulation of the electron transport chain (ETC) and the preserved or enhanced capacity of mitochondrial fatty acid oxidation, which stimulates ROS overproduction within different ETC components upstream of cytochrome c oxidase. However, non-ETC sources of ROS, in particular, fatty acid β-oxidation, appear to produce more ROS in hepatic metabolic diseases. Endoplasmic reticulum stress and NADPH oxidase alterations are also associated with NAFLD, but the degree of their contribution to oxidative stress in NAFLD remains unclear. Increased ROS generation induces changes in insulin sensitivity and in the expression and activity of key enzymes involved in lipid metabolism. Moreover, the interaction between redox signaling and innate immune signaling forms a complex network that regulates inflammatory responses. Based on the mechanistic view described above, this review summarizes the mechanisms that may account for the excessive production of ROS, the potential mechanistic roles of ROS that drive NAFLD progression, and therapeutic interventions that are related to oxidative stress.

中文翻译：

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氧化应激在非酒精性脂肪肝疾病发病机理中的作用。

非酒精性脂肪性肝病（NAFLD）已成为全球最常见的慢性肝病，并且与氧化应激的存在密切相关。脂质代谢紊乱会导致肝脏脂质蓄积，从而影响不同的活性氧（ROS）生成器，包括线粒体，内质网和NADPH氧化酶。线粒体功能主要通过电子传输链（ETC）的下调以及线粒体脂肪酸氧化能力的维持或增强来适应NAFLD，这会刺激细胞色素C氧化酶上游不同ETC组件内的ROS过度产生。但是，非ETC ROS来源，特别是脂肪酸β-氧化，似乎在肝代谢疾病中产生更多的ROS。内质网应激和NADPH氧化酶的改变也与NAFLD相关，但是它们对NAFLD氧化应激的贡献程度仍不清楚。ROS产生的增加引起胰岛素敏感性以及参与脂质代谢的关键酶的表达和活性的变化。而且，氧化还原信号和先天免疫信号之间的相互作用形成调节炎症反应的复杂网络。基于上述机理的观点，本综述总结了可能导致ROS过度产生的机理，驱动NAFLD进展的ROS的潜在机理作用以及与氧化应激相关的治疗性干预措施。ROS产生的增加引起胰岛素敏感性以及参与脂质代谢的关键酶的表达和活性的变化。此外，氧化还原信号和先天性免疫信号之间的相互作用形成调节炎症反应的复杂网络。基于上述机理的观点，本综述总结了可能导致ROS过度产生的机理，驱动NAFLD进展的ROS的潜在机理作用以及与氧化应激相关的治疗性干预措施。ROS产生的增加引起胰岛素敏感性以及参与脂质代谢的关键酶的表达和活性的变化。而且，氧化还原信号和先天免疫信号之间的相互作用形成调节炎症反应的复杂网络。基于上述机理的观点，本综述总结了可能导致ROS过度产生的机理，驱动NAFLD进展的ROS的潜在机理作用以及与氧化应激相关的治疗性干预措施。