BNIP3 localizes to the outer mitochondrial membrane, has been demonstrated to be extensively involved in abnormalities to mitochondrial metabolic function and dynamicsand in non-alcoholic fatty liver disease (NAFLD). However, its role in NAFLD under hypoxia remains unclear. This study aimed to investigate the expression and the role of BNIP3 in NAFLD under hypoxia, and explore its involvement in regulating NAFLD mitophagy, fatty acid β-oxidation both in vivo and in vitro. BNIP3-mediated mitophagy level was analyzed using real-time quantitative polymerase chain reaction, Western blotting, immunofluorescence and electron microscopy. The role of BNIP3 in fatty acid β-oxidation was evaluated using lipid droplet staining, triglyceride content determination, and cellular energy metabolism. The results showed that compared with the HFD-2200 m, the body weight, inflammatory liver injury, and lipid deposition were significantly reduced in the HFD-4500 m group (P < 0.05), but autophagy and mitophagy were increased, and the expression of the mitophagy receptor BNIP3 was increased (P < 0.05). Compared to the control group, BNIP3 knockdown in the hypoxia group resulted in decreased levels of CPT1, ATGL, and p-HSL in lipid-accumulating hepatocytes, lipid droplet accumulation and triglyceride content increased (P < 0.05). Moreover, the ability of lipid-accumulating hepatocytes to oxidize fatty acids was reduced by BNIP3 knockdown in the hypoxia group (P < 0.05). Therefore, it can be concluded that, in NAFLD mice under hypoxia, BNIP3-mediated mitophagy promotes fatty acid β-oxidation. This study elucidated the role of BNIP3 in promoting fatty acid β-oxidation in NAFLD under hypoxia, and suggests BNIP3 may serve as a novel potential therapeutic target for NAFLD.

BNIP3 定位于线粒体外膜，已被证明广泛参与线粒体代谢功能和动力学异常以及非酒精性脂肪肝疾病 (NAFLD)。然而，其在缺氧条件下 NAFLD 中的作用仍不清楚。本研究旨在探讨缺氧条件下BNIP3在NAFLD中的表达及作用，探讨其在体内外调控NAFLD线粒体自噬、脂肪酸β-氧化的作用。使用实时定量聚合酶链反应、蛋白质印迹、免疫荧光和电子显微镜分析BNIP3介导的线粒体自噬水平。使用脂滴染色、甘油三酯含量测定和细胞能量代谢评估BNIP3在脂肪酸β-氧化中的作用。结果显示，与 HFD-2200 m 组相比，HFD-4500 m 组体重、炎性肝损伤、脂质沉积明显减轻（ P < 0.05），但自噬和线粒体自噬增加，且线粒体自噬受体BNIP3增加(P <0.05)。与对照组相比，低氧组 BNIP3 敲低导致脂质堆积肝细胞中 CPT1、ATGL 和 p-HSL 水平降低，脂滴积累和甘油三酯含量增加（P < 0.05）。此外，低氧组中 BNIP3 敲低可降低脂质堆积肝细胞氧化脂肪酸的能力（P < 0.05）。因此，可以得出结论，在缺氧的NAFLD小鼠中，BNIP3介导的线粒体自噬促进了脂肪酸β-氧化。该研究阐明了BNIP3在缺氧条件下NAFLD中促进脂肪酸β-氧化的作用，并表明BNIP3可能作为NAFLD的新的潜在治疗靶点。