Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury
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 catab...
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MDPI AG
2022-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/10/1706 |
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| author | Guiling Wu Yanjie Guo Min Li Chenhan Li Yanzhen Tan Yueyang Li Jia Li Li Wang Xing Zhang Feng Gao |
| author_facet | Guiling Wu Yanjie Guo Min Li Chenhan Li Yanzhen Tan Yueyang Li Jia Li Li Wang Xing Zhang Feng Gao |
| author_sort | Guiling Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:09:47Z |
| format | Article |
| id | doaj.art-8558393577e74531b76b2c8f9af050f0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:09:47Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8558393577e74531b76b2c8f9af050f02023-11-23T10:28:29ZengMDPI AGCells2073-44092022-05-011110170610.3390/cells11101706Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic InjuryGuiling Wu0Yanjie Guo1Min Li2Chenhan Li3Yanzhen Tan4Yueyang Li5Jia Li6Li Wang7Xing Zhang8Feng Gao9Key Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Cardiology, Chinese PLA General Hospital, Beijing 100853, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaKey Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi’an 710032, ChinaLong-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.https://www.mdpi.com/2073-4409/11/10/1706exerciseBCAA catabolismmyocardial infarctionPP2Cmcardioprotection |
| spellingShingle | Guiling Wu Yanjie Guo Min Li Chenhan Li Yanzhen Tan Yueyang Li Jia Li Li Wang Xing Zhang Feng Gao Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury Cells exercise BCAA catabolism myocardial infarction PP2Cm cardioprotection |
| title | Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury |
| title_full | Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury |
| title_fullStr | Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury |
| title_full_unstemmed | Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury |
| title_short | Exercise Enhances Branched-Chain Amino Acid Catabolism and Decreases Cardiac Vulnerability to Myocardial Ischemic Injury |
| title_sort | exercise enhances branched chain amino acid catabolism and decreases cardiac vulnerability to myocardial ischemic injury |
| topic | exercise BCAA catabolism myocardial infarction PP2Cm cardioprotection |
| url | https://www.mdpi.com/2073-4409/11/10/1706 |
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