极长链脂肪酸在代谢相关脂肪性肝病发病机制中的作用

孔佳琪; 任婷婷; 刘瑞; 周贵忠; 朱传龙

doi:10.12449/JCH260830

极长链脂肪酸在代谢相关脂肪性肝病发病机制中的作用

DOI: 10.12449/JCH260830

孔佳琪¹,
任婷婷¹,
刘瑞^{1, 2},
周贵忠²,
朱传龙^{1, 2, , ,}

1.
南京医科大学第一附属医院感染病科，南京 210029
2.
海南医科大学第二附属医院感染病与热带病科，海口 570100

基金项目:

国家自然科学基金 (82472167);

海南省临床医学研究中心项目 (LCYX202204);

海南省临床医学研究中心项目 (LCYX202306);

海南省临床医学研究中心项目 (LCYX202408);

江苏自然科学基金 (BK20241982)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：任婷婷负责检索文献及整理；孔佳琪负责文章撰写及图片绘制；刘瑞、周贵忠负责课题设计和文章修改；朱传龙负责拟定思路及最终定稿。

详细信息

通信作者:
朱传龙， zhuchuanlong@jsph.org.cn （ORCID： 0000-0001-6557-1654）

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出版历程
- 收稿日期: 2026-01-21
- 录用日期: 2026-03-16
- 出版日期: 2026-08-25

The role of very-long-chain fatty acids in the pathogenesis of metabolic dysfunction-associated fatty liver disease

Jiaqi Kong¹,
Tingting Ren¹,
Rui Liu^{1, 2},
Guizhong Zhou²,
Chuanlong Zhu^{1, 2
, ,
,}

1.
Department of Infectious Diseases，The First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，China
2.
Department of Infectious and Tropical Diseases，The Second Affiliated Hospital of Hainan Medical University，Haikou 570100，China

Research funding:

National Natural Science Foundation of China (82472167);

Science and Technology Plan of Hainan Province （Clinical Research Center） (LCYX202204);

Science and Technology Plan of Hainan Province （Clinical Research Center） (LCYX202306);

Science and Technology Plan of Hainan Province （Clinical Research Center） (LCYX202408);

Natural Science Foundation of Jiangsu Province (BK20241982)

More Information

Corresponding author: Zhu Chuanlong， zhuchuanlong@jsph.org.cn （ORCID： 0000-0001-6557-1654）

摘要

摘要: 代谢相关脂肪性肝病作为一种最常见的慢性肝脏疾病，已成为全球性的重大健康问题。其核心病理事件是肝脏内脂质的过度累积，继而引发脂毒性，通过介导内质网应激、氧化应激、细胞器功能障碍和铁死亡等，最终导致细胞凋亡、坏死及炎症级联反应，推动单纯性肝脂肪变性向脂肪性肝炎和纤维化进展。在此过程中，极长链脂肪酸（VLCFA）作为细胞膜和脂质代谢中的重要组成部分，其在脂毒性机制中的作用逐渐受到关注。本文综述VLCFA在脂质代谢过程及脂毒性机制中的作用，重点阐述VLCFA通过关键蛋白参与代谢调控、破坏细胞膜诱发氧化应激，及其代谢产物与衍生物驱动炎症反应，最终促进代谢相关脂肪性肝病进展的分子机制。
- 代谢相关脂肪性肝病 /
- 脂肪酸类 /
- 病理过程
Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most common chronic liver disease， and it has become a major global health issue. Excessive lipid accumulation in the liver is the core pathological event of MAFLD， which triggers lipotoxicity and leads to cell apoptosis， necrosis， and inflammatory cascades by mediating endoplasmic reticulum stress， oxidative stress， organelle dysfunction， and ferroptosis， thereby promoting the progression of simple hepatic steatosis to steatohepatitis and fibrosis. In this process， very-long-chain fatty acids （VLCFAs）， as essential components of cell membranes and lipid metabolism， have attracted increasing attention for their role in lipotoxicity mechanisms. This article reviews the role of VLCFAs in lipid metabolism processes and lipotoxicity mechanisms， focusing on how VLCFAs participate in metabolic regulation through key proteins and disrupt cell membranes to induce oxidative stress， and how their metabolites and derivatives drive inflammatory responses， ultimately promoting the progression of MAFLD.
- Metabolic Dysfunction-Associated Fatty Liver Disease /
- Fatty Acids /
- Pathologic Processes

HTML全文

注： VLCFA，极长链脂肪酸；ELOVL1，极长链脂肪酸延长酶1；SCD1，硬脂酰辅酶A去饱和酶1；UPR，未折叠蛋白应答；PERK，蛋白质激酶RNA样内质网激酶；IRE1α，肌醇需求酶1α；ATF6，激活转录因子6；ETC，电子传递链；ROS，活性氧；mPTP，线粒体通透性转换孔；Caspase，胱天蛋白酶；NLRP3，核苷酸结合寡聚结构域样受体家族热蛋白结构域相关蛋白3；IL-1β，白细胞介素1β；IL-18，白细胞介素18；MASH，代谢相关脂肪性肝炎；MAFLD，代谢相关脂肪性肝病。

图 1 VLCFA通过细胞器互作网络驱动MAFLD进展的机制

Figure 1. Schematic diagram of the mechanism by which VLCFA drive MAFLD progression through organelle interaction networks

下载: 全尺寸图片幻灯片

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