代谢相关脂肪性肝病肝纤维化的代谢重编程机制

陈苑彤; 窦婧; 李雪; 苏比努尔·库尔班; 王晓忠

doi:10.12449/JCH251225

代谢相关脂肪性肝病肝纤维化的代谢重编程机制

DOI: 10.12449/JCH251225

1.
新疆医科大学第四临床医学院，乌鲁木齐 830000
2.
新疆维吾尔自治区中医医院肝病科，乌鲁木齐 830000

基金项目:

新疆维吾尔自治区自然科学基金 (2024D01C121);

新疆医科大学科学研究所开放课题 (YXYJLSI20240301)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：陈苑彤负责撰写稿件；窦婧负责拟定选题；李雪、苏比努尔·库尔班负责文献检索；王晓忠负责审定终稿。

详细信息

通信作者:
王晓忠， wxz125@sina.com （ORCID： 0000-0002-9389-9232）

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出版历程
- 收稿日期: 2025-04-17
- 录用日期: 2025-06-13
- 出版日期: 2025-12-25

The metabolic reprogramming mechanisms of liver fibrosis in metabolic associated fatty liver disease

1.
The Fourth Clinical Medical College of Xinjiang Medical University，Urumqi 830000，China
2.
Department of Hepatology，Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region，Urumqi 830000，China

Research funding:

Natural Science Foundation of Xinjiang Uygur Autonomous Region (2024D01C121);

Open Research Project of the Institute of Science,Xinjiang Medical University (YXYJLSI20240301)

More Information

Corresponding author: WANG Xiaozhong， wxz125@sina.com （ORCID： 0000-0002-9389-9232）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）肝纤维化的发病率逐年上升，其持续进展最终可导致肝硬化甚至肝癌。糖代谢、脂代谢及蛋白质代谢的途径发生改变并为肝星状细胞（HSC）的活化提供必要的能量支持，从而促进肝纤维化进展。现有研究阐明了上述代谢重编程在调控HSC活化中的具体作用机制，如HSC活化与糖酵解增强、乳酸微环境形成、脂肪酸β氧化抑制、脂毒性累积、谷氨酰胺分解增强以及蛋白质稳定性和S-腺苷蛋氨酸（SAM）水平变化等，且乳酸微环境形成、脂毒性累积以及SAM水平等变化可加速肝纤维化进展。本文系统综述了MAFLD肝纤维化中代谢途径的变化以及相互间的协同作用，以期为揭示该病的发病机制和开发新型治疗策略提供重要理论依据。
- 代谢相关脂肪性肝病 /
- 肝纤维化 /
- 肝星状细胞 /
- 代谢重编程
Abstract: There has been a gradual increase in the incidence rate of metabolic associated fatty liver disease （MAFLD）-related liver fibrosis year by year， and its progression may eventually lead to liver cirrhosis and even liver cancer. There are changes in the pathways of glucose metabolism， lipid metabolism， and protein metabolism， which provide necessary energy support for the activation of hepatic stellate cells （HSC）， thereby promoting the progression of liver fibrosis. Existing studies have clarified the specific mechanisms of metabolic reprogramming in regulating the activation of HSC such as the activation of HSC and enhanced glycolysis， the formation of a lactic acid microenvironment， the inhibition of fatty acid β-oxidation， the accumulation of lipotoxicity， enhanced glutamine decomposition， and changes in protein stability and S-adenosylmethionine （SAM）. Moreover， the formation of a lactic acid microenvironment， the accumulation of lipotoxicity， and changes in SAM can accelerate the progression of liver fibrosis. This article systematically reviews the changes in related metabolic pathways in MAFLD-related liver fibrosis and the synergistic effect between them， in order to provide an important theoretical basis for revealing the pathogenesis of this disease and developing new treatment strategies.
- Metabolic Associated Fatty Liver Disease /
- Liver Fibrosis /
- Hepatic Stellate Cell /
- Metabolic Reprogramming

HTML全文

注： GLUT1，葡萄糖转运蛋白1；Glc，葡萄糖；HK2，己糖激酶2；PFKFB3，果糖2，6双磷酸酶3；Pyr，丙酮酸；Lac，乳酸；AcCoA，乙酰辅酶A；ACC，乙酰辅酶A羧化酶；ATP，三磷酸腺苷；DNL，从头脂肪生成；BAMBI，BMP和激活素膜结合抑制剂；aHSC，活化的HSC；RORA，维甲酸相关孤儿受体α；PKM2，丙酮酸激酶M2。

图 1 MAFLD肝纤维化的代谢重编程机制

Figure 1. Metabolic reprogramming mechanism of liver fibrosis in metabolic associated fatty liver disease

下载: 全尺寸图片幻灯片

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