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Effect of chronic exercise in healthy young male adults: a metabolomic analysis.
Cardiovascular Research ( IF 10.2 ) Pub Date : 2020-04-01 , DOI: 10.1093/cvr/cvaa051
Yen Chin Koay 1, 2 , Kelly Stanton 1, 3 , Vivian Kienzle 1 , Mengbo Li 2, 4 , Jean Yang 2, 4 , David S Celermajer 1, 3 , John F O'Sullivan 1, 2, 3
Affiliation  

Abstract
Aims
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.
Methods and results
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.
Conclusion
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.


中文翻译:

长期运动对健康年轻男性的影响:代谢组学分析。

摘要
宗旨
研究在控制饮食、睡眠和体育活动等生活方式因素的健康年轻男性中,对 80 天运动干预的代谢适应。
方法和结果
本研究涉及 2015 年对 52 名年轻、成年、男性、新入伍士兵进行 80 天有氧和力量锻炼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。数据分析在 2019 年 3 月至 2019 年 8 月期间进行。我们分析了 80 天运动干预结束时与基线相比的代谢组学变化,以及代谢物变化与临床参数变化的关联。运动训练计划后,全球新陈代谢发生了巨大变化。脂肪酸和酮体底物是锻炼肌肉使用的关键燃料,随着有氧运动的增加,血浆中的脂肪酸和酮体底物急剧减少。许多类别的代谢底物发生了非常显着的变化,包括脂质、酮体、精氨酸代谢物、内源性大麻素、核苷酸、蛋白水解标志物、脂肪酸氧化产物、微生物组衍生代谢物、氧化还原应激标志物和凝血底物。对于统计分析,配对使用 t检验且 Bonferroni 调整的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)(最近显示可预测缺乏对运动的代谢反应)跟踪对运动的适应不良代谢变化;那些增加的DMGV水平有增加的几个心血管危险因素; DMGV 水平的变化与体脂(P  = 0.049)、总胆固醇和 LDL 胆固醇(P  = 0.003 和P  = 0.007)和收缩压(P = 0.006)。这项研究得到了国防部和退伍军人事务部人类研究伦理委员会的批准,并获得了每个受试者的书面知情同意。
结论
这项精心设计的研究首次揭示了代谢适应慢性运动训练的真实程度和程度,可用于心脏代谢疾病的新治疗策略。扩展最近关于 DMGV 对久坐、超重个体的预测效用的报告,我们发现它也是年轻、健康、健康男性对运动的不良代谢反应的有用标志。
更新日期:2020-04-01
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