《生命科学》 2026, 38(3): 444-453

亚精胺改善代谢性疾病的研究进展

王泷彬^1,2 , 艾锐泽³ , 张翊娟^1,2 , 黄启超⁴ , 樊晓霞^1,* , 季乐乐^2,*

¹延安大学医学院基础医学院，延安716000 ²空军军医大学基础医学院基础医学国家级实验教学示范 中心，西安710032 ³空军军医大学基础医学院学员二大队，西安710032 ⁴空军军医大学基础医学院生 理与病理生理学教研室，西安710032

摘　要：

亚精胺（spermidine）是一种广泛存在于生物体内的多胺类化合物，在衰老研究领域备受关注。它通过诱导细胞自噬、促进eIF5A的hypusine修饰以及抑制炎症反应与细胞凋亡等多种途径，发挥延缓细胞衰老、维持机体稳态等作用。随着亚精胺在代谢调控中的作用被逐步揭示，其在代谢性疾病防治中的潜力也愈发凸显。多项研究显示，膳食补充亚精胺能够有效延缓糖尿病和心血管疾病等多种代谢性疾病的发生与发展。本综述系统总结亚精胺在代谢性疾病中的作用机制与研究前沿，进而探讨其作为营养干预靶点的应用前景与临床干预潜力，以期为相关疾病的防治提供新思路。

通讯作者：樊晓霞 , Email:fanxiaoxia01@163.com 季乐乐 , Email:jilele@fmmu.edu.cn

Research progress on spermidine for the amelioration of metabolic diseases

WANG Shuang-Bin^1,2 , AI Rui-Ze³ , ZHANG Yi-Juan^1,2 , HUANG Qi-Chao⁴ , FAN Xiao-Xia^1,* , JI Le-Le^2,*

¹School of Basic Medical Sciences, Medical College of Yan’an University, Yan’an 716000, China ²National Demonstration Center for Experimental Basic Medical Science Education, Fourth Military Medical University, Xi’an 710032, China ³Second Battalion of Basic Medical College Students, Fourth Military Medical University, Xi’an 710032, China ⁴Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an 710032, China

Abstract:

Metabolic disorders comprise a group of diseases characterized by disturbances in energy metabolism, including major public health challenges such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Spermidine, a ubiquitous, naturally occurring polyamine, is essential for maintaining physiological health and sustaining metabolic balance. In the context of ageing research, spermidine has been shown to exert diverse and significant biological effects. Recent findings have increased interest in its capacity to  improve metabolic health. Epidemiological evidence indicates a strong inverse association between dietary spermidine intake and the incidence of diabetes and cardiovascular diseases. Notably, spermidine concentrations decline progressively with age, particularly in elderly populations with a high prevalence of metabolic disorders. However, the mechanisms by which spermidine influences metabolic disease, as well as its therapeutic potential, remain incompletely understood. This review aims to systematically examine the biological roles of spermidine in metabolic disorders and elucidate the molecular mechanisms involved, providing a foundation for novel preventive and therapeutic strategies. This review first outlines the biosynthetic and transport pathways of spermidine, establishing a framework for understanding the origins and regulation of its biological functions. In vivo, the mammalian spermidine pool is derived from three primary sources: dietary intake, de novo biosynthesis, and gut microbiotaderived production. Its distribution and regulation rely on coordinated enzymatic  cascades and membrane transport systems. The review then summarizes and discusses the key molecular mechanisms underlying spermidine’s putative protective actions, which include: stimulation of autophagy to remove misfolded proteins and damaged organelles; serving as a substrate for eIF5A hypusination, thereby modulating translation and cell proliferation; suppression of pro-inflammatory signaling pathways such as NF-κB to reduce tissue inflammation; inhibition of apoptotic process and reinforcement of antioxidant  defense to promote cell survival; and optimization of mitochondrial function to enhance metabolic efficiency. These interconnected processes establish spermidine as a critical regulator of metabolic stability. Through these mechanisms, spermidine demonstrates broad prophylactic and therapeutic potential across a spectrum of metabolic disorders. In obesity, it  promotes weight management by activating adipose tissue lipolysis, enhancing thermogenesis in brown adipose tissue, and  improving gut microbiota composition and intestinal barrier function. In diabetes, it contributes to glycaemic control by improving peripheral insulin sensitivity, preserving pancreatic β-cell function, and alleviating vascular endothelial  inflammatory injury. In MASLD, it mitigates hepatic steatosis and inflammation by enhancing fatty acid oxidation, reducing lipid accumulation, and directly improving mitochondrial function, thereby retarding the progression of fibrosis. In cardiovascular diseases, it confers protection against hypertension and atherosclerosis through multiple pathways, including  inducing cardiomyocyte autophagy to improve cardiac function and elasticity, modulating blood lipid profiles, inhibiting platelet aggregation, and stabilizing atherosclerotic plaques. In conclusion, spermidine supports metabolic homeostasis through a multifaceted, synergistic network of molecular actions, offering promising avenues for intervention in multiple metabolic disorders, as evidenced by preclinical research. However, its effects are influenced by cellular context and environmental factors, and translation to clinical practice is challenged by limited human trial data, uncertain dose-response parameters, and potential context-dependent adverse effects. Future advancements will require robust clinical studies informed by a comprehensive understanding of its complex molecular interactions and systems-level biology, with the ultimate goal of defining optimal therapeutic parameters and advancing spermidine as a viable strategy for metabolic disease prevention and treatment.

Communication Author：FAN Xiao-Xia , Email:fanxiaoxia01@163.com JI Le-Le , Email:jilele@fmmu.edu.cn