《生命科学》 2025, 37(3): 233-241

肥胖防治的潜在靶点：中脑星形胶质细胞源性神经营养因子

陈　方 , 刘　彦 , 吴鑫淼 , 李良鸣^* , 杨文琦^*

广州体育学院国家体育总局运动技战术诊断与机能评定重点实验室，广州 510500

摘　要：

中脑星形胶质细胞源性神经营养因子(MANF) 除神经保护作用外，还是一种内质网应激诱导蛋白，关键的结构域使其具有抑制内质网应激和减轻内质网应激诱导的凋亡的作用。慢性内质网应激既是肥胖诱发的重要病理改变，又可进一步加剧能量失衡、扰乱糖脂代谢、促进炎症反应，进而推动肥胖及其相关慢病的进展。越来越多的证据表明，MANF 的表达受营养状况的调节，并且在调控能量代谢、减轻炎症反应方面扮演着重要的角色，是肥胖及其相关慢性代谢性疾病防治的潜在靶点。本文将介绍MANF 的表达与分泌、结构与功能，并从能量稳态、糖脂代谢和炎症反应方面总结MANF 在肥胖中的作用。

通讯作者：李良鸣 , Email:liliangming@gzsport.edu.cn 杨文琦 , Email:shuixianyuhuai@126.com

potential target for obesity prevention and treatment: midbrain astrocyte-derived neurotrophic factor

CHEN Fang , LIU Yan , WU Xin-Miao , LI Liang-Ming^* , YANG Wen-Qi^*

Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou 510500, China

Abstract:

In addition to its neuroprotective effects, mesencephalic astrocyte-derived neurotrophic factor (MANF) is recognized as an endoplasmic reticulum stress-inducing protein. Its key structural domain enables it to inhibit endoplasmic reticulum stress (ERS) and alleviate ERS-induced apoptosis. Chronic ERS is not only a critical pathological change induced by obesity, but can also further exacerbate energy imbalance, disrupt glucose and lipid metabolism, and promote inflammatory responses, thereby advancing the progression of obesity and its related chronic diseases. Growing evidence indicates that the expression of MANF is regulated by nutritional status, and MANF plays a vital role in maintaining energy homeostasis, regulating glucose and lipid metabolism, and reducing inflammatory responses. Thus, it presents a potential target for the management of obesity and obesity associated chronic metabolic diseases. This article discusses the expression and secretion, as well as the structure and function of MANF. Additionally, we summarize the role of MANF in obesity concerning energy homeostasis, glucose and lipid metabolism, and inflammatory responses.

Communication Author：LI Liang-Ming , Email:liliangming@gzsport.edu.cn YANG Wen-Qi , Email:shuixianyuhuai@126.com