Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury.
Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury.
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运动增强支链氨基酸分解代谢并降低心脏对心肌缺血性损伤的脆弱性
作者：
长期运动诱导的代谢适应在运动提供的心脏益处中占据中心位置。新出现的证据表明，支链氨基酸（BCAA）分解代谢缺陷有助于在多种心脏代谢疾病的心功能障碍。然而，BCAA catenaries在运动提供的心脏益处中的作用仍然未知。在这里，我们表明，运动可以改善支链氨基酸的catalysts，从而减少心肌缺血损伤的心脏脆弱性。运动增加了人类（男性青少年运动员）和小鼠（经过8周的游泳干预）的循环BCAA水平。它增加了线粒体定位的2C型丝氨酸-苏氨酸蛋白磷酸酶（PP 2Cm）的表达，这是调节BCAA催化剂的关键酶，并减少了小鼠心脏中BCAA的积累，表明BCAA催化剂增加。药理学促进BCAA催化剂保护小鼠心脏免受永久结扎左冠状动脉降支引起的心肌梗死（MI）。虽然心脏特异性PP 2Cm基因敲除对心脏结构和功能对运动的适应性没有显着影响，但它减弱了运动对MI的心脏保护作用。从机制上讲，运动减轻了支链氨基酸的积累，随后灭活了哺乳动物的雷帕霉素在MI心脏的目标。这些结果表明，运动提高了BCAA的催化剂，保护心脏免受心肌缺血损伤，加强了运动在促进心脏健康中的作用。
Long-term exercise-induced metabolic adaptations occupy a central position in exercise-afforded cardiac benefits. Emerging evidence suggests that branched-chain amino acid (BCAA) catabolic defect contributes to cardiac dysfunction in multiple cardiometabolic diseases. However, the role of BCAA catabolism in exercise-afforded cardiac benefits remains unknown. Here, we show that exercise improves BCAA catabolism and thus reduce cardiac vulnerability to myocardial ischemic injury. Exercise increased circulating BCAA levels in both humans (male adolescent athletes) and mice (following an 8-week swimming intervention). It increased the expression of mitochondrial localized 2C-type serine-threonine protein phosphatase (PP2Cm), a key enzyme in regulating BCAA catabolism, and decreased BCAA accumulation in mouse hearts, indicating an increase in BCAA catabolism. Pharmacological promotion of BCAA catabolism protected the mouse heart against myocardial infarction (MI) induced by permanent ligation of the left descending coronary artery. Although cardiac-specific PP2Cm knockout showed no significant effects on cardiac structural and functional adaptations to exercise, it blunted the cardioprotective effects of exercise against MI. Mechanistically, exercise alleviated BCAA accumulation and subsequently inactivated the mammalian target of rapamycin in MI hearts. These results showed that exercise elevated BCAA catabolism and protected the heart against myocardial ischemic injury, reinforcing the role of exercise in the promotion of cardiac health.
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影响因子：
2.1
作者：
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通讯作者：
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29
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11.7
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影响因子：
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作者：
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