Abstract
Multiple studies endorsed the positive effect of regular exercise on mental and physical health. However, the molecular mechanisms underlying training-induced fitness in combination with personal life-style remain largely unexplored. Circulating biomarkers such as microRNAs (miRNAs) offer themselves for studying systemic and cellular changes since they can be collected from the bloodstream in a low-invasive manner. In Homo sapiens miRNAs are known to regulate a substantial number of protein-coding genes in a post-transcriptional manner and hence are of great interest to understand differential gene expression profiles, offering a cost-effective mechanism to study molecular training adaption, and connecting the dots from genomics to observed phenotypes. Here, we investigated molecular expression patterns of 2549 miRNAs in whole-blood samples from healthy and untrained adult participants of a cross-over study, consisting of eight weeks of endurance training, with several sessions per week, followed by 8 weeks of washout and another 8 weeks of running, using microarrays. Participants were randomly assigned to one of the two study groups, one of which administered carbohydrates before each session in the first training period, and switching the treatment group for the second training period. During running sessions clinical parameters as heartbeat frequency were recorded. This information was extended with four measurements of maximum oxygen uptake (VO max) for each participant. We observed that multiple circulating miRNAs show expression changes after endurance training, leveraging the capability to separate the blood samples by training status. To this end, we demonstrate that most of the variance in miRNA expression can be explained by both common and known biological and technical factors. Our findings highlight six distinct clusters of miRNAs, each exhibiting an oscillating expression profile across the four study timepoints, that can effectively be utilized to predict phenotypic VO max levels. In addition, we identified miR-532-5p as a candidate marker to determine personal alterations in physical training performance on a case-by-case analysis taking the influence of a carbohydrate-rich nutrition into account. In literature, miR-532-5p is known as a common down-regulated miRNA in diabetes and obesity, possibly providing a molecular link between cellular homeostasis, personal fitness levels, and health in aging. We conclude that circulating miRNA expression can be altered due to regular endurance training, independent of the carbohydrate (CHO) availability in the training timeframe. Further validation studies are required to confirm the role of exercise-affected miRNAs and the extraordinary function of miR-532-5p in modulating the metabolic response to a high availability of glucose.
Highlights
The positive effects of sports activity on physical and mental health as well as the cardiovascular effects of training have been widely characterized [1,2,3]
This motivates the question whether miRNA signatures being indicative of fitness levels after repeated endurance exercise, commonly measured via increasing values of maximal oxygen consumption VO2 max, exist and whether this is related to a varying abundance of glucose in blood [12]
Our findings are based on a randomized cross-over study that consists of 23 participants, randomly split into two groups [17]
Summary
The positive effects of sports activity on physical and mental health as well as the cardiovascular effects of training have been widely characterized [1,2,3]. High blood-glucose availability affects the drop in cellular ATP availability under physical stress conditions, which in turn determines the timing of AMP-activated protein kinase (AMPK) activation [14] To this end, AMPK is of particular interest because it is thought to protect the cell from ATP shortage and to function as the initial starting point in a signal cascade that governs the physiological adaption to regular physical exercising [15,16]. AMPK is of particular interest because it is thought to protect the cell from ATP shortage and to function as the initial starting point in a signal cascade that governs the physiological adaption to regular physical exercising [15,16] This motivates the question whether miRNA signatures being indicative of fitness levels after repeated endurance exercise, commonly measured via increasing values of maximal oxygen consumption VO2 max, exist and whether this is related to a varying abundance of glucose in blood [12]
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