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脂质代谢重编程在代谢相关脂肪性肝病进展中的作用机制

程新月,  罗磊,  刘熔,  曹帅兵,  禄保平

引用本文:
Citation:

脂质代谢重编程在代谢相关脂肪性肝病进展中的作用机制

DOI: 10.12449/JCH260923
基金项目: 

国家自然科学基金 (82305074);

河南省中医药科学研究专项课题 (2024ZY2156);

河南省中医药科学研究专项课题 (2025ZY1031);

河南省科技攻关项目 (262102310449)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:程新月负责撰写论文;罗磊负责课题设计及修改论文;刘熔、曹帅兵负责文献检索及整理;禄保平负责拟定写作思路及最后定稿。
详细信息
    通信作者:

    禄保平, lbp1921@sohu.com (ORCID: 0000-0002-3707-2185)

Mechanism of action of lipid metabolic reprogramming in the progression of metabolic dysfunction-associated fatty liver disease

Research funding: 

National Natural Science Foundation of China (82305074);

Special Project for Traditional Chinese Medicine Research of Henan Province (2024ZY2156);

Special Project for Traditional Chinese Medicine Research of Henan Province (2025ZY1031);

Henan Key Research and Development Program (262102310449)

More Information
    Corresponding author: Lu Baoping, lbp1921@sohu.com (ORCID: 0000-0002-3707-2185)
  • 摘要: 代谢相关脂肪性肝病(MAFLD)是全球患病率最高的慢性肝病,其疾病谱涵盖从肝脂肪变性到代谢相关脂肪性肝炎、肝纤维化、肝硬化及肝细胞癌的演进过程。近年来,MAFLD的研究范式已从“脂质堆积”转向“脂质代谢重编程”,其作为疾病发生进展的关键环节,受多维度分子网络调控。本综述系统梳理MAFLD中脂质代谢重编程的分子机制:解析脂质代谢紊乱的核心作用,重点阐述内质网-线粒体接触等细胞器互作失调的介导作用;聚焦脂毒性诱发的铁死亡等新型程序性细胞死亡,揭示其加剧肝损伤的通路;整合腺苷一磷酸活化的蛋白质激酶、核转录因子红系2相关因子2等关键信号通路的调控网络,探讨液-液相分离、微蛋白调控等新兴机制。展望了靶向脂质代谢重编程关键节点的潜在治疗策略,为MAFLD的病理机制研究及精准干预提供理论依据。

     

  • 注: MAFLD,代谢相关脂肪性肝病;AMPK,腺苷一磷酸活化的蛋白质激酶;Nrf2,核转录因子红系2相关因子2;p38/MAPK,p38丝裂原活化蛋白激酶;JAK/STAT,Janus激酶/信号转导与转录激活因子;Cidec,细胞死亡诱导DFFA样效应蛋白C;UFD1s,剪接体泛素融合降解蛋白1样蛋白。

    图  1  MAFLD脂质代谢重编程与病理机制概览

    Figure  1.  Overview of lipid metabolism reprogramming and pathological mechanisms in MAFLD

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