Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy
Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy
复制标题
运动通过改善糖尿病心肌病发展过程中的线粒体功能障碍和维持能量稳态来增强心脏功能
DOI：
10.1007/s00109-019-01861-2
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发表时间：
2020-01-02
影响因子：
4.7
通讯作者：
Liu, Jingjin
中科院分区：
文献类型：
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作者：
Wang, Shawn Yongshun;Zhu, Siyu;Liu, Jingjin
糖尿病性心肌病（DCM）是糖尿病患者发病和死亡的主要原因。氧化应激产生的活性氧（ROS）在DCM的发生发展中起着重要作用。DCM涉及能量代谢异常，从而减少能量产生。据报道，在DCM的发展过程中，运动可以有效地保护心脏免受ROS的积累。我们推测AMPK/PGC-1α轴可能在运动诱导的生物能量代谢和有氧呼吸中对糖尿病心肌病的氧化应激参数起关键作用。采用链脲佐菌素/高脂饮食小鼠建立糖尿病模型，目的是评估运动对心功能、线粒体氧化能力、线粒体功能和PGC-1α心脏表达的影响。饲喂高脂饲料的小鼠给予MO-siPGC-1α或AMPK抑制剂。分析线粒体结构和Warburg效应与有氧呼吸之间转换的影响。运动改善了糖尿病小鼠心脏的血压和收缩功能障碍。在线粒体功能研究中也观察到运动的有益影响，反映在氧化磷酸化水平增强，膜电位增加，ROS水平和耗氧量降低。另一方面，PGC-1α的消耗减弱了运动对线粒体功能增强的作用。此外，PGC-1α可能负责逆转Warburg效应对有氧呼吸，从而增强线粒体代谢和能量平衡。在这项研究中，我们证明了运动对糖尿病阶段能量代谢从脂肪酸氧化转变为葡萄糖氧化的保护作用。这些数据表明，运动可以通过改善线粒体功能和减少代谢紊乱来有效改善糖尿病性心肌病。
Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances.