PMID- 31500139 OWN - NLM STAT- MEDLINE DCOM- 20200611 LR - 20200611 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 8 IP - 9 DP - 2019 Sep 6 TI - Systematic Assessment of Blood-Borne MicroRNAs Highlights Molecular Profiles of Endurance Sport and Carbohydrate Uptake. LID - 10.3390/cells8091045 [doi] LID - 1045 AB - 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 23 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 2 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 2 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. FAU - Kern, Fabian AU - Kern F AD - Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. fabian.kern@ccb.uni-saarland.de. FAU - Ludwig, Nicole AU - Ludwig N AD - Department of Human Genetics, Saarland University Hospital, 66421 Homburg, Germany. n.ludwig@mx.uni-saarland.de. AD - Center for Human and Molecular Biology, Saarland University Hospital, 66421 Homburg, Germany. n.ludwig@mx.uni-saarland.de. FAU - Backes, Christina AU - Backes C AD - Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. c.backes@mx.uni-saarland.de. FAU - Maldener, Esther AU - Maldener E AD - Department of Human Genetics, Saarland University Hospital, 66421 Homburg, Germany. Esther.Maldener@uks.eu. AD - Center for Human and Molecular Biology, Saarland University Hospital, 66421 Homburg, Germany. Esther.Maldener@uks.eu. FAU - Fehlmann, Tobias AU - Fehlmann T AD - Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. tobias.fehlmann@ccb.uni-saarland.de. FAU - Suleymanov, Artur AU - Suleymanov A AD - Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. artur.suleymanov@uni-saarland.de. FAU - Meese, Eckart AU - Meese E AD - Department of Human Genetics, Saarland University Hospital, 66421 Homburg, Germany. Eckart.Meese@uks.eu. AD - Center for Human and Molecular Biology, Saarland University Hospital, 66421 Homburg, Germany. Eckart.Meese@uks.eu. FAU - Hecksteden, Anne AU - Hecksteden A AD - Department of Sports Medicine, Saarland University, 66123 Saarbrucken, Germany. a.hecksteden@mx.uni-saarland.de. FAU - Keller, Andreas AU - Keller A AD - Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. andreas.keller@ccb.uni-saarland.de. AD - Center for Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. andreas.keller@ccb.uni-saarland.de. AD - School of Medicine Office, Stanford University, Stanford, CA-94305, USA. andreas.keller@ccb.uni-saarland.de. AD - Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA-94305, USA. andreas.keller@ccb.uni-saarland.de. FAU - Meyer, Tim AU - Meyer T AD - Department of Sports Medicine, Saarland University, 66123 Saarbrucken, Germany. tim.meyer@mx.uni-saarland.de. LA - eng PT - Journal Article DEP - 20190906 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Biomarkers) RN - 0 (Carbohydrates) RN - 0 (Circulating MicroRNA) RN - 0 (MicroRNAs) RN - S88TT14065 (Oxygen) SB - IM MH - Adult MH - Biomarkers/metabolism MH - Carbohydrate Metabolism/genetics MH - Carbohydrates/genetics MH - Circulating MicroRNA MH - Cross-Over Studies MH - Exercise/*physiology MH - Female MH - Healthy Volunteers MH - Humans MH - Male MH - MicroRNAs/analysis/blood/*genetics MH - Muscle, Skeletal/metabolism MH - Oxygen/metabolism MH - Oxygen Consumption/*genetics MH - Physical Endurance/physiology MH - Running/physiology PMC - PMC6770460 OTO - NOTNLM OT - circulating biomarker OT - full-blood measurements OT - glucose nutrition OT - homeostasis OT - microRNA OT - microarray OT - physical exercising OT - randomized cross-over study OT - sncRNAs COIS- The authors declare no conflict of interest. EDAT- 2019/09/11 06:00 MHDA- 2020/06/12 06:00 PMCR- 2019/09/01 CRDT- 2019/09/11 06:00 PHST- 2019/08/01 00:00 [received] PHST- 2019/08/31 00:00 [revised] PHST- 2019/09/04 00:00 [accepted] PHST- 2019/09/11 06:00 [entrez] PHST- 2019/09/11 06:00 [pubmed] PHST- 2020/06/12 06:00 [medline] PHST- 2019/09/01 00:00 [pmc-release] AID - cells8091045 [pii] AID - cells-08-01045 [pii] AID - 10.3390/cells8091045 [doi] PST - epublish SO - Cells. 2019 Sep 6;8(9):1045. doi: 10.3390/cells8091045.