自噬在肥胖及相关代谢疾病中的作用

doi:10.3870/j.issn.1672-8009.2026.03.011

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (3): 316-324.doi: 10.3870/j.issn.1672-8009.2026.03.011

自噬在肥胖及相关代谢疾病中的作用

李尔干^1#, 邓丽^2#, 吕凤如^2#, 黎友琴³, 冯政民², 周嘉裕^2Δ, 李妍^1Δ, 冯钟徽^4Δ

¹西南民族大学畜牧兽医学院成都市,610000
西南交通大学²生命科学与工程学院,³医学院成都市,610000
⁴成都市第三人民医院肥胖与代谢医工结合实验室成都市,610000

收稿日期:2026-04-23 发布日期:2026-06-01
通讯作者: 冯钟徽(E-mail:fengzh.2008@tsinghua.org.cn),周嘉裕(E-mail:spinezhou@home.swjtu.edu.cn),李妍(E-mail:lyvet2004@163.com)
作者简介:#:共同第一作者
基金资助:
国家自然科学基金(No.82202007),成都市第三人民医院临床研究项目(No.2023PI22、No.CSY-YN-01-2023-039),四川省自然科学基金(No.2023NSFSC0739)

Role of Autophagy in Obesity and Related Metabolic Diseases

LI Ergan^1#, DENG Li^2#, LV Fengru^2#, LI Youqin³, FENG Zhengmin², ZHOU Jiayu^2Δ, LI Yan^1Δ, FENG Zhonghui^4Δ

¹School of Animal Science and Veterinary Medicine,Southwest Minzu University,Chengdu,610000,China
²School of Life Sciences and Engineering,³School of Medicine,Southwest Jiaotong University,Chengdu,610000,China
⁴Laboratory of Medical and Engineering Approaches to Obesity and Metabolism,Chengdu Third People's Hospital,Chengdu,610000,China

Received:2026-04-23 Published:2026-06-01
Contact: FENG Zhonghui(E-mail:fengzh.2008@tsinghua.org.cn),ZHOU Jiayu(E-mail:spinezhou@home.swjtu.edu.cn),LI Yan(E-mail:lyvet2004@163.com)
About author:#:These authors contributed equally as first author.
Supported by:
National Natural Science Foundation of China(No.82202007),the Third People’s Hospital of Chengdu Clinical Research Program(No.2023PI22,No.CSY-YN-01-2023-039),the Natural Science Foundation of Sichuan Province(No.2023NSFSC0739)

摘要/Abstract

摘要： 肥胖是当今全球范围内十分突出、危害极大的公共卫生危机,其实质上是能量摄入与消耗长期失衡的结果,与此直接相关的有中枢摄食调控、脂肪组织代谢及全身炎症反应诸种复杂网络。自噬是一种高度保守、功能明确的细胞内降解途径,能清除受损细胞器、蛋白聚集体及脂滴,因而天然参与能量回收及代谢调控。具体而言,在脂肪组织中,自噬在白色脂肪中促进脂肪生成及脂质储存,在棕色/米色脂肪中参与线粒体清除及白化过程,调节产热功能,同时在脂肪组织巨噬细胞中通过降低线粒体活性氧、抑制NLRP3炎症小体活化来弱化促炎反应,从而调控组织炎症。更为重要的是,下丘脑POMC和AgRP神经元中的自噬可直接调控神经肽的加工、分泌,是中枢控制食欲及能量消耗极为重要的分子开关。肥胖相关自噬基因在脂肪生成、产热调控、炎症反应及神经元功能中都具有明确而关键的作用,其失调必然导致脂质堆积、胰岛素抵抗及慢性炎症,形成中枢-外周相互强化的代谢紊乱网络。正因如此,基于自噬调控机制的营养干预、药理激活及miRNA介导的精准干预都显示出改善肥胖及相关代谢紊乱的巨大潜力。因此,系统、严谨地厘清自噬在脂肪组织、中枢神经系统及全身代谢调控中的作用,有利于从分子层面阐明肥胖的机制,从而设计有效的组织特异性干预策略。

关键词: 自噬, 肥胖, 脂肪组织, 下丘脑, 胰岛素抵抗, 代谢性炎症, 治疗靶点

Abstract: Obesity is a prominent and highly detrimental public health crisis worldwide.Its essence lies in a chronic imbalance between energy intake and expenditure,directly involving complex networks of central appetite regulation,adipose tissue metabolism,and systemic inflammation.Autophagy is a highly conserved and well-defined intracellular degradation pathway that clears damaged organelles,protein aggregates,and lipid droplets,thereby intrinsically participating in energy recycling and metabolic regulation.Specifically,in adipose tissue,autophagy promotes adipogenesis and lipid storage in white adipose tissue,participates in mitochondrial clearance and the whitening process in brown/beige adipose tissue to modulate thermogenesis,and attenuates pro-inflammatory responses in adipose tissue macrophages by reducing mitochondrial reactive oxygen species and inhibiting NLRP3 inflammasome activation,thereby regulating tissue inflammation.More importantly,autophagy in hypothalamic POMC and AgRP neurons directly regulates neuropeptide processing and secretion,thus serving as a critical molecular switch for central control of appetite and energy expenditure.Obesity-related autophagy genes play clear and essential roles in adipogenesis,thermogenic regulation,inflammatory responses,and neuronal function;their dysregulation inevitably leads to lipid accumulation,insulin resistance,and chronic inflammation,forming a central-peripheral,mutually reinforcing network of metabolic dysregulation.Consequently,nutritional interventions,pharmacological activation,and miRNA-mediated precision interventions based on autophagic regulatory mechanisms all show great promise for ameliorating obesity and related metabolic disorders.Therefore,systematically and rigorously elucidating the role of autophagy in adipose tissue,the central nervous system,and systemic metabolic regulation will help clarify the molecular mechanisms underlying obesity and,more importantly,facilitate the design of effective tissue-specific intervention strategies.

Key words: autophagy, obesity, adipose tissue, hypothalamus, insulin resistance, metabolic inflammation, therapeutic targets

中图分类号:

R589
Q255

李尔干, 邓丽, 吕凤如, 黎友琴, 冯政民, 周嘉裕, 李妍, 冯钟徽. 自噬在肥胖及相关代谢疾病中的作用[J]. 医学分子生物学杂志, 2026, 23(3): 316-324.

LI Ergan, DENG Li, LV Fengru, LI Youqin, FENG Zhengmin, ZHOU Jiayu, LI Yan, FENG Zhonghui. Role of Autophagy in Obesity and Related Metabolic Diseases[J]. Journal of Medical Molecular Biology, 2026, 23(3): 316-324.

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自噬在肥胖及相关代谢疾病中的作用

Role of Autophagy in Obesity and Related Metabolic Diseases

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