Koay Yen Chin, Stanton Kelly, Kienzle Vivian, Li Mengbo, Yang Jean, Celermajer David S, O'Sullivan John F
Heart Research Institute, Sydney, NSW, Australia.
The University of Sydney, Charles Perkins Centre, Sydney, NSW, Australia.
Cardiovasc Res. 2021 Jan 21;117(2):613-622. doi: 10.1093/cvr/cvaa051.
To examine the metabolic adaptation to an 80-day exercise intervention in healthy young male adults where lifestyle factors such as diet, sleep, and physical activities are controlled.
This study involved cross-sectional analysis before and after an 80-day aerobic and strength exercise intervention in 52 young, adult, male, newly enlisted soldiers in 2015. Plasma metabolomic analyses were performed using liquid chromatography, tandem mass spectrometry. Data analyses were performed between March and August 2019. We analysed changes in metabolomic profiles at the end of an 80-day exercise intervention compared to baseline, and the association of metabolite changes with changes in clinical parameters. Global metabolism was dramatically shifted after the exercise training programme. Fatty acids and ketone body substrates, key fuels used by exercising muscle, were dramatically decreased in plasma in response to increased aerobic fitness. There were highly significant changes across many classes of metabolic substrates including lipids, ketone bodies, arginine metabolites, endocannabinoids, nucleotides, markers of proteolysis, products of fatty acid oxidation, microbiome-derived metabolites, markers of redox stress, and substrates of coagulation. For statistical analyses, a paired t-test was used and Bonferroni-adjusted P-value of <0.0004 was considered to be statistically significant. The metabolite dimethylguanidino valeric acid (DMGV) (recently shown to predict lack of metabolic response to exercise) tracked maladaptive metabolic changes to exercise; those with increases in DMGV levels had increases in several cardiovascular risk factors; changes in DMGV levels were significantly positively correlated with increases in body fat (P = 0.049), total and LDL cholesterol (P = 0.003 and P = 0.007), and systolic blood pressure (P = 0.006). This study was approved by the Departments of Defence and Veterans' Affairs Human Research Ethics Committee and written informed consent was obtained from each subject.
For the first time, the true magnitude and extent of metabolic adaptation to chronic exercise training are revealed in this carefully designed study, which can be leveraged for novel therapeutic strategies in cardiometabolic disease. Extending the recent report of DMGV's predictive utility in sedentary, overweight individuals, we found that it is also a useful marker of poor metabolic response to exercise in young, healthy, fit males.
在饮食、睡眠和体育活动等生活方式因素得到控制的情况下，研究健康年轻男性成年人对为期80天运动干预的代谢适应情况。
本研究对2015年入伍的52名年轻成年男性新兵进行了为期80天的有氧和力量运动干预前后的横断面分析。使用液相色谱-串联质谱法进行血浆代谢组学分析。数据分析于2019年3月至8月进行。我们分析了与基线相比，80天运动干预结束时代谢组学谱的变化，以及代谢物变化与临床参数变化之间的关联。运动训练计划后，整体代谢发生了显著变化。随着有氧适能的提高，血浆中运动肌肉使用的关键燃料脂肪酸和酮体底物显著减少。包括脂质、酮体、精氨酸代谢物、内源性大麻素、核苷酸、蛋白水解标记物、脂肪酸氧化产物、微生物群衍生代谢物、氧化还原应激标记物和凝血底物在内的许多类代谢底物都发生了高度显著的变化。统计分析采用配对t检验，Bonferroni校正P值<0.0004被认为具有统计学意义。代谢物二甲基胍基戊酸（DMGV）（最近显示可预测对运动的代谢反应缺乏）跟踪了对运动的适应不良代谢变化；DMGV水平升高的人多种心血管危险因素增加；DMGV水平的变化与体脂增加（P = 0.049）、总胆固醇和低密度脂蛋白胆固醇增加（P = 0.003和P = 0.007）以及收缩压升高（P = 0.006）显著正相关。本研究经国防部和退伍军人事务部人类研究伦理委员会批准，并获得了每位受试者的书面知情同意。
在这项精心设计的研究中首次揭示了对慢性运动训练代谢适应的真实程度和范围，这可为心脏代谢疾病的新型治疗策略提供依据。扩展了最近关于DMGV在久坐、超重个体中的预测效用的报告，我们发现它也是年轻、健康、体能良好男性对运动代谢反应不良的有用标志物。
