The Comparative Methylome and Transcriptome After Change of Direction Compared to Straight Line Running Exercise in Human Skeletal Muscle.

Autor:	Maasar MF; Stem Cells, Aging and Molecular Physiology Unit, Exercise Metabolism and Adaptation Research Group, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom., Turner DC; Stem Cells, Aging and Molecular Physiology Unit, Exercise Metabolism and Adaptation Research Group, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.; Institute for Science and Technology in Medicine, School of Pharmacy and Bioengineering, Keele University, Staffordshire, United Kingdom., Gorski PP; Institute for Science and Technology in Medicine, School of Pharmacy and Bioengineering, Keele University, Staffordshire, United Kingdom.; Institute for Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway., Seaborne RA; Stem Cells, Aging and Molecular Physiology Unit, Exercise Metabolism and Adaptation Research Group, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.; Centre for Genomics and Child Health, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom., Strauss JA; Exercise Metabolism and Adaptation Research Group, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom., Shepherd SO; Exercise Metabolism and Adaptation Research Group, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom., Cocks M; Exercise Metabolism and Adaptation Research Group, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom., Pillon NJ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Zierath JR; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Hulton AT; Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom., Drust B; School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United Kingdom., Sharples AP; Institute for Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2021 Feb 19; Vol. 12, pp. 619447. Date of Electronic Publication: 2021 Feb 19 (Print Publication: 2021).
DOI:	10.3389/fphys.2021.619447
Abstrakt:	The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g., high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in five male sport team members using a repeated measures design of: (1) change of direction (COD) versus; (2) straight line (ST) running exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 min and 24 h post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed × distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) exertion measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 min and 24 h post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 min post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We also confirmed increased gene expression of VEGFA , and considerably larger increases in the expression of canonical metabolic genes PPARGC1A (that encodes PGC1- α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via COD exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Maasar, Turner, Gorski, Seaborne, Strauss, Shepherd, Cocks, Pillon, Zierath, Hulton, Drust and Sharples.)
Databáze:	MEDLINE
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