Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark.
Cell Mol Life Sci. 2018 Sep;75(18):3313-3327. doi: 10.1007/s00018-018-2860-6. Epub 2018 Jun 23.
Non-alcoholic fatty liver disease (NAFLD) is currently the world's most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition exceeding lipid disposal, i.e., the uptake of fatty acids and de novo lipogenesis surpassing fatty acid oxidation and export. In NAFLD, hepatic uptake and de novo lipogenesis are increased, while a compensatory enhancement of fatty acid oxidation is insufficient in normalizing lipid levels and may even promote cellular damage and disease progression by inducing oxidative stress, especially with compromised mitochondrial function and increased oxidation in peroxisomes and cytochromes. While lipid export initially increases, it plateaus and may even decrease with disease progression, sustaining the accumulation of lipids. Fueled by lipo-apoptosis, hepatic steatosis leads to systemic metabolic disarray that adversely affects multiple organs, placing abnormal lipid metabolism associated with NAFLD in close relation to many of the current life-style-related diseases.
非酒精性脂肪性肝病（NAFLD）是目前世界上最常见的肝脏疾病，估计影响多达四分之一的人口。NAFLD 的特征是肝脂肪变性，与多种有害影响和死亡率增加有关。本综述探讨了 NAFLD 中肝脂肪变性的分子机制，重点关注导致肝脏脂质稳态的四大主要途径。肝脂肪变性是脂质摄取超过脂质处置的结果，即脂肪酸摄取和从头合成超过脂肪酸氧化和输出。在 NAFLD 中，肝摄取和从头合成增加，而脂肪酸氧化的代偿性增强不足以使脂质水平正常化，甚至可能通过诱导氧化应激促进细胞损伤和疾病进展，特别是在存在线粒体功能受损和过氧化物酶体和细胞色素中氧化增加的情况下。尽管脂质输出最初增加，但随着疾病的进展，它会趋于平稳甚至下降，从而维持脂质的积累。在脂凋亡的推动下，肝脂肪变性导致全身代谢紊乱，对多个器官产生不利影响，使与 NAFLD 相关的异常脂质代谢与许多当前与生活方式相关的疾病密切相关。
