运动干预NAFLD的分子机制研究述评——基于ROS调节UPRmt的线粒体毒性兴奋效应  

Mechanisms in Exercise Intervening NAFLD:Mitohormesis of ROS-induced UPRmt

作　　者：张媛[1,2] 文立 丁树哲 ZHANG Yuan;WEN Li;DING Shuzhe(School of Sports and Health,Nanjing Sport Institute,Nanjing 210014,China;The Exercise Translational Medicine Centre of Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University,Shanghai 200240,China;Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education,East China Normal University,Shanghai 200241,China;College of Physical Education and Health,East China Normal University,Shanghai 200241,China)

机构地区：[1]南京体育学院运动健康学院,江苏南京210014 [2]上海交通大学系统生物医学研究院运动转化医学中心,上海200240 [3]华东师范大学青少年健康评价与运动干预教育部重点实验室,上海200241 [4]华东师范大学体育与健康学院,上海200241

出　　处：《体育科学》2022年第7期74-84,共11页China Sport Science

基　　金：国家自然科学基金青年科学基金项目(32000839);江苏省自然科学基金面上项目(BK20191473);中国博士后基金项目(2018M641990);江苏省“青蓝工程”资助项目(苏教师函[2021]11号)。

摘　　要：非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是被严重低估的全球重大健康威胁,目前尚无美国食品药品监督管理局(Food and Drug Administration,FDA)批准治疗NAFLD的药物,深入研究其发病机理、探索治疗策略迫在眉睫。氧化应激是NAFLD发展的核心环节,线粒体活性氧(reactive oxygen species,ROS)生成与稳态维持与NAFLD密切相关。有氧运动或脂质沉积可改变细胞ROS水平,而不同ROS水平对线粒体未折叠蛋白反应(UPRmt)的调节作用表现为线粒体毒性兴奋效应,即对线粒体稳态的轻度扰动会促进与协调线粒体-细胞核之间的“对话”,降低细胞对外来刺激源的敏感性,提高细胞抵御刺激的能力。未来有关运动干预NAFLD的研究将进一步探索运动应激下ROS通过elF2α-ATF4/ATF5-CHOP轴调节UPRmt的分子机制,以寻找提高线粒体蛋白折叠能力、促进线粒体因子分泌、提升线粒体自我修复功能、维持稳态的有效途径,为NAFLD的防治提供理论依据。Non-alcoholic fatty liver disease(NAFLD) is a severe but underestimated health threat in the world, and there is no FDA approved effective pharmacologic agents currently. Therefore, it is urgent to study its pathogenesis and explore treatment strategies.Research shows that oxidative stress is implicated in the development of NAFLD, and the mitochondria ROS production and homeostasis are crucial for the prevention and treatment of NAFLD. Aerobic exercise or lipid deposition can change the ROS level in cells, and the regulation of different ROS levels on mitochondrial unfolded protein response(UPRmt) is defined as“mitohormesis”. The slight disturbance in mitochondrial homeostasis will promote the “crosstalk” between the coordinating mitochondria and the nucleus, and then reduce the sensitivity of cells to external stimuli and improve the ability of cells to resist stimuli. Future research should investigate the molecular mechanism of exercise induced UPRmt activation and mitokines secretion through ROS regulated elF2α-ATF4/5-CHOP pathway, and to illuminate the effect of exercise on ROS-UPRmt regulatory mechanism and mitochondrial homeostasis maintenance, thus providing theoretical references for the prevention and control of NAFLD.

关 键 词：非酒精性脂肪肝 运动 氧化应激 线粒体毒性兴奋效应 

分 类 号：G804.5[文化科学—运动人体科学]