Xu Hui-Li, Wan Sheng-Rong, An Ying, Wu Qi, Xing Yi-Hang, Deng Chen-Hao, Zhang Ping-Ping, Long Yang, Xu Bu-Tuo, Jiang Zong-Zhe
Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China.
Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan, PR China.
Cell Death Discov. 2024 Sep 7;10(1):399. doi: 10.1038/s41420-024-02168-z.
Nonalcoholic fatty liver disease (NAFLD) is a group of chronic liver disease which ranges from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and is characterized by lipid accumulation, inflammation activation, fibrosis, and cell death. To date, a number of preclinical studies or clinical trials associated with therapies targeting fatty acid metabolism, inflammatory factors and liver fibrosis are performed to develop effective drugs for NAFLD/NASH. However, few therapies are cell death signaling-targeted even though the various cell death modes are present throughout the progression of NAFLD/NASH. Here we summarize the four types of cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis in the NAFLD and the underlying molecular mechanisms by which the pathogenic factors such as free fatty acid and LPS induce cell death in the pathogenesis of NAFLD. In addition, we also review the effects of cell death-targeted therapies on NAFLD. In summary, our review provides comprehensive insight into the roles of various cell death modes in the progression of NAFLD, which we hope will open new avenues for therapeutic intervention.
非酒精性脂肪性肝病（NAFLD）是一组慢性肝病，范围从单纯性脂肪变性（NAFL）到非酒精性脂肪性肝炎（NASH），其特征是脂质蓄积、炎症激活、纤维化和细胞死亡。迄今为止，已经开展了许多与针对脂肪酸代谢、炎症因子和肝纤维化的疗法相关的临床前研究或临床试验，以开发用于NAFLD/NASH的有效药物。然而，尽管在NAFLD/NASH的整个进展过程中存在各种细胞死亡模式，但很少有疗法是以细胞死亡信号为靶点的。在此，我们总结了NAFLD中的四种细胞死亡类型，包括凋亡、坏死性凋亡、焦亡和铁死亡，以及游离脂肪酸和脂多糖等致病因素在NAFLD发病机制中诱导细胞死亡的潜在分子机制。此外，我们还综述了针对细胞死亡的疗法对NAFLD的影响。总之，我们的综述全面深入地探讨了各种细胞死亡模式在NAFLD进展中的作用，希望这将为治疗干预开辟新的途径。
