O-连接β-N-乙酰葡萄糖胺糖基化修饰在代谢相关脂肪性肝病中的作用

刘素彤; 张丽慧; 赵晴; 马唯琛; 朱万怡; 刘鸣昊; 赵文霞

doi:10.12449/JCH260623

O-连接β-N-乙酰葡萄糖胺糖基化修饰在代谢相关脂肪性肝病中的作用

DOI: 10.12449/JCH260623

刘素彤^{1, 2, , ,},
张丽慧^{1, 2},
赵晴^{1, 2},
马唯琛¹,
朱万怡¹,
刘鸣昊^{1, 2},
赵文霞^{1, 2}

1.
河南中医药大学第一附属医院肝病区域诊疗中心，郑州 450000
2.
河南中医药大学中西医防治重大疾病河南省协同创新中心，郑州 450046

基金项目:

国家自然科学基金青年项目 (82205086);

河南省中医药科学研究专项 (2022JDZX114);

第九届中国科协青年人才托举工程 (2023QNRC001);

河南省中医学“双一流”创建科学研究专项 (HSRP-DFCTCM-2023-5-13);

河南省博士后基金 (HN2024080)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：刘素彤负责撰写论文及图片整理；张丽慧、赵晴等负责修改论文；马唯琛、朱万怡等负责文献检索及整理；赵文霞、刘鸣昊等负责拟定写作思路及最后定稿。

详细信息

通信作者:
刘素彤， qingteng1026@126.com （ORCID： 0000-0002-9124-1111）

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出版历程
- 收稿日期: 2025-10-27
- 录用日期: 2025-12-15
- 出版日期: 2026-06-25

Role of O-linked β-N-acetylglucosamine modification in metabolic associated fatty liver disease

Sutong LIU^{1, 2
, ,
,},
Lihui ZHANG^{1, 2},
Qing ZHAO^{1, 2},
Weichen MA¹,
Wanyi ZHU¹,
Minghao LIU^{1, 2},
Wenxia ZHAO^{1, 2}

1.
Regional Diagnosis and Treatment Center for Hepatology，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China
2.
Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine in Henan Province，Henan University of Chinese Medicine，Zhengzhou 450046，China

Research funding:

National Natural Science Foundation of China (82205086);

Specialized Standards for Henan Provincial Traditional Chinese Medicine Scientific Research Projects (2022JDZX114);

Young Elite Scientists Sponsorship Program by CAST (2023QNRC001);

Henan Province Traditional Chinese Medicine “Double First-Class” to Create a Scientific Research Project (HSRP-DFCTCM-2023-5-13);

Henan Province Postdoctoral Fund (HN2024080)

More Information

Corresponding author: LIU Sutong， qingteng1026@126.com （ORCID： 0000-0002-9124-1111）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）作为全球范围内发病率迅速增长的慢性肝病，其复杂的发病机制与O-连接β-N-乙酰葡萄糖胺糖基化（O-GlcNAc）修饰密切相关。O-GlcNAc修饰作为一种动态可逆的蛋白质翻译后修饰，主要由O-GlcNAc转移酶和O-GlcNAc糖苷酶调控。O-GlcNAc修饰能驱动肝脂肪变性、加重胰岛素抵抗以及损害线粒体功能，加剧代谢紊乱，促进炎症反应，推动MAFLD向代谢相关脂肪性肝炎及肝纤维化发展。本文系统综述了O-GlcNAc修饰在MAFLD发生发展中的最新研究进展，旨在为深入理解MAFLD的病理机制及开发有效治疗策略提供理论支持和研究方向。
- 代谢相关脂肪性肝病 /
- O-连接β-N-乙酰葡萄糖胺糖基化 /
- 蛋白质加工，转译后
Abstract: Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.
- Metabolic Associated Fatty Liver Disease /
- O-linked β-N-Acetylglucosamine /
- Protein Processing， Post-Translational

HTML全文

注： HUP，己糖胺生物合成途径；UDP-GlcNAc，尿苷二磷酸-N-乙酰葡糖胺；O-GlcNAc，O-连接β-N-乙酰葡萄糖胺糖基化；OGT，O-GlcNAc转移酶；OGA，O-GlcNAc糖苷酶；IRS-1/2，胰岛素受体底物1/2；Akt，蛋白激酶B；FASN，脂肪酸合酶；SREBP-1c，甾醇调节元件结合蛋白1c；ChREBP，碳水化合物应答元件结合蛋白；NF-κB，核因子κB；ECT，电子传递链；ROS，活性氧。

图 1 O-GlcNAc修饰在MAFLD中的机制变化

Figure 1. The mechanism changes of O-GlcNAc glycosylation modification in metabolic associated fatty liver disease

下载: 全尺寸图片幻灯片

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