自噬途径降解肝脏脂滴的研究进展

王蓉芝; 王琳雳; 焦靖雯; 于云飞; 李宝龙

doi:10.12449/JCH240931

自噬途径降解肝脏脂滴的研究进展

DOI: 10.12449/JCH240931

黑龙江中医药大学药物安全性评价中心，哈尔滨 150040

基金项目:

国家自然科学基金面上项目 (81573135);

黑龙江省自然科学基金 (LH2023H056);

黑龙江省博士后科研启动项目 (LBH-Q21042)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：王琳雳、焦靖雯、于云飞负责收集资料；李宝龙、王蓉芝负责课题设计，资料分析，撰写论文，修改论文并最终定稿。

详细信息

通信作者:
李宝龙， lbl73@163.com （ORCID： 0009-0008-1930-2224）

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出版历程
- 收稿日期: 2023-12-21
- 录用日期: 2024-02-21
- 出版日期: 2024-09-25

Research advances in the degradation of hepatic lipid droplets through the autophagy pathway

Center for Safety Evaluation of drugs，Heilongjiang University of Chinese Medicine，Harbin 150040，China

Research funding:

General Project of National Natural Science Foundation of China (81573135);

Natural Science Foundation of Heilongjiang Province of China (LH2023H056);

Heilongjiang Postdoctoral Research Initiation Program (LBH-Q21042)

More Information

Corresponding author: LI Baolong， lbl73@163.com （ORCID： 0009-0008-1930-2224）

摘要

摘要: 自噬是一种高度保守的细胞降解途径，可通过“脂噬”过程来降解脂滴。脂噬可以选择性地识别脂类物质并将其降解，促进β氧化，进而维持细胞内脂质代谢的平衡状态。肝脏通过脂噬信号通路或关键分子来调控脂滴代谢，进而降低肝脏脂肪变性，改善非酒精性脂肪性肝病。本文总结归纳了巨自噬、分子伴侣介导的自噬和微自噬样3种自噬途径降解肝脏脂滴的最新研究进展，AMPK/mTOR-ULK1、ATGL-SIRT1、FGF21-JMJD3、Akt作为调控脂噬过程的主要信号通路，有助于维持肝脂质代谢稳态，能够为临床预防和治疗非酒精性脂肪性肝病提供新思路。
- 非酒精性脂肪性肝病 /
- 自噬 /
- 脂类代谢 /
- 病理过程
Abstract: Autophagy is a highly conserved cellular degradation pathway that degrades lipid droplets through a process called “lipophagy”. Lipophagy can selectively recognize lipid substances and degrade them， promoting β oxidation and thereby maintaining the balance of intracellular lipid metabolism. The liver regulates lipid droplet metabolism through lipophagy signaling pathways or key molecules， thereby alleviating hepatic steatosis and improving nonalcoholic fatty liver disease （NAFLD）. This article reviews the latest advances in the degradation of hepatic lipid droplets through the three autophagic pathways of macroautophagy， molecular chaperone-mediated autophagy， and microautophagy. The major signaling pathways of AMPK/mTOR-ULK1， ATGL-SIRT1， FGF21-JMJD3， and Akt are involved in the regulation of the lipophagy process and help to maintain the homeostasis of lipid metabolism in the liver， so as to provide new ideas for clinical prevention and treatment of NAFLD.
- Non-alcoholic Fatty Liver Disease /
- Autophagy /
- Lipid Metabolism /
- Pathologic Processes

HTML全文

图 1 巨自噬信号通路示意图

Figure 1. Schematic diagram of the macroautophagy signaling pathway

下载: 全尺寸图片幻灯片

图 2 巨自噬和CMA参与脂质代谢示意图

Figure 2. Schematic diagram of the involvement of macroautophagy and CMA in lipid metabolism

下载: 全尺寸图片幻灯片

表 1 不同自噬形式参与脂滴降解的分子机制

Table 1. Molecular mechanisms of different forms of autophagy involved in lipid droplet degradation

自噬类型	关键分子机制及通路	作用	生物	文献
巨自噬	ULK1/ATG1	启动自噬体的形成	哺乳动物、酵母	［14］
	mTOR-ULK1	抑制脂噬	哺乳动物	［15］
	AMPK-ULK1	促进脂噬	哺乳动物	［15］
	TFEB	脂噬主要调节因子	哺乳动物	［16］
	HLH-30、MXL-3	调节脂噬	秀丽隐杆线虫	［16］
	FgATG15（酵母ATG15同源物）	参与脂滴分解	禾谷镰刀菌	［17］
	OsATG7（酵母ATG7同源物）	参与脂滴分解	水稻	［18］
	ATG蛋白	识别脂滴，促进自噬体的形成	酵母、哺乳动物、植物、微藻	［19-21］
	SNARE蛋白	介导自噬体膜的扩展/闭合	酵母、哺乳动物	［22-23］
	SQSTM1/p62	桥接脂滴与吞噬泡	哺乳动物	［24］
	Rab GTP酶	介导脂滴的募集	哺乳动物	［25］
CMA	HSC70	识别并结合脂滴	哺乳动物	［26］
CMA	LAMP-2A	结合脂滴并将其移至溶酶体内	哺乳动物	［26］
微自噬	ATG6和ATG14	形成脂滴募集位点	酵母	［27］
微自噬	ESCRT蛋白Vps27	将脂滴转移到液泡	酵母	［28］

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