Role of Autophagy in Obesity and Related Metabolic Diseases

doi:10.3870/j.issn.1672-8009.2026.03.011

Abstract

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

CLC Number:

R589
Q255

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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