National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, PR China.
Biochem Biophys Res Commun. 2013 Apr 19;433(4):408-14. doi: 10.1016/j.bbrc.2013.02.118. Epub 2013 Mar 26.
Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H2O2 and TNF-α, two typical "second hit" factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.
非酒精性脂肪性肝病（NAFLD）已成为慢性肝病的主要病因，但 NAFLD 的发病机制尚不完全清楚。本研究旨在确定自噬是否在 NAFLD 的发病机制中起作用。我们发现，游离脂肪酸暴露后肝癌细胞中的自噬水平升高，自噬体数量增加证实了这一点。然而，肝癌细胞暴露于 H2O2 和 TNF-α（两种典型的“二次打击”因素）会增加自噬的起始，但抑制自噬流。自噬的抑制使细胞对促凋亡刺激敏感。总之，我们的结果表明，自噬在 NAFLD 的发病机制中起保护作用，自噬的损伤可能导致肝脏更严重的损伤。这些发现将有助于理解 NAFLD 的发病机制，并可能为预防和治疗 NAFLD 提供策略。
