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

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohd-Firdaus Maasar ◽  
Daniel C. Turner ◽  
Piotr P. Gorski ◽  
Robert A. Seaborne ◽  
Juliette A. Strauss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Axon Guidance ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Meta Analysis ◽  
Post Exercise ◽  
Change Of Direction ◽  
Running Exercise ◽  
Repeated Measures Design ◽  
Straight Line

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.

scholarly journals The methylome and comparative transcriptome after high intensity sprint exercise in human skeletal muscle

2020 ◽  
Author(s):  
Mohd Firdaus Maasar ◽  
Daniel C. Turner ◽  
Piotr P. Gorski ◽  
Robert A. Seaborne ◽  
Juliette A. Strauss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Axon Guidance ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Meta Analysis ◽  
Post Exercise ◽  
Sprint Exercise ◽  
Change Of Direction ◽  
Repeated Measures Design ◽  
Sprint Running

AbstractThe methylome and transcriptome signature following exercise that is physiologically and metabolic 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 undertook two different sport/exercise relevant high-intensity sprint running protocols in humans using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) sprint exercise. We took skeletal muscle biopsies from the vastus lateralis 30 minutes and 24 hours post exercise followed by 850K methylation arrays and comparative analysis with recent sprint and acute aerobic exercise meta-analysis transcriptomes. Despite matched intensity (speed x distance and number of accelerations/decelerations) between COD and ST exercise, COD exercise elicited greater movement (GPS Playerload™), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) loading compared with ST exercise. The exercise response alone across both conditions evoked extensive alterations in the methylome immediately post and 24 hrs after exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST sprint exercise, particularly enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. A finding that was more prominent immediately post exercise. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of the genes altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we discovered 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 confirmed increased mRNA expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PGC1-α and NR4A3, 3 hrs post COD vs. ST exercise. Overall, we demonstrate that increased physiological load via change of direction sprint exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise. These data imply that introducing changes in direction into high intensity running protocols could serve as an important modulator of a favourable epigenomic and transcriptomic landscape in response to exercise in athletes and trigger greater skeletal muscle remodelling through enhanced gene expression.

scholarly journals Antioxidants Facilitate High–intensity Exercise IL–15 Expression in Skeletal Muscle

2018 ◽  
Vol 40 (01) ◽  
pp. 16-22 ◽  
Author(s):  
Alberto Pérez-López ◽  
Marcos Martin-Rincon ◽  
Alfredo Santana ◽  
Ismael Perez-Suarez ◽  
Cecilia Dorado ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Acute Hypoxia ◽  
High Intensity Exercise ◽  
Oxygen Deficit ◽  
Post Exercise ◽  
Sprint Exercise

AbstractInterleukin (IL)-15 stimulates mitochondrial biogenesis, fat oxidation, glucose uptake and myogenesis in skeletal muscle. However, the mechanisms by which exercise triggers IL-15 expression remain to be elucidated in humans. This study aimed at determining whether high-intensity exercise and exercise-induced RONS stimulate IL-15/IL-15Rα expression and its signaling pathway (STAT3) in human skeletal muscle. Nine volunteers performed a 30-s Wingate test in normoxia and hypoxia (PIO2=75 mmHg), 2 h after placebo or antioxidant administration (α-lipoic acid, vitamin C and E) in a randomized double-blind design. Blood samples and muscle biopsies (vastus lateralis) were obtained before, immediately after, and 30 and 120 min post-exercise. Sprint exercise upregulated skeletal muscle IL-15 protein expression (ANOVA, P=0.05), an effect accentuated by antioxidant administration in hypoxia (ANOVA, P=0.022). In antioxidant conditions, the increased IL-15 expression at 120 min post-exercise (33%; P=0.017) was associated with the oxygen deficit caused by the sprint (r=–0.54; P=0.020); while, IL-15 and Tyr705-STAT3 AUCs were also related (r=0.50; P=0.036). Antioxidant administration promotes IL-15 protein expression in human skeletal muscle after sprint exercise, particularly in severe acute hypoxia. Therefore, during intense muscle contraction, a reduced PO2 and glycolytic rate, and possibly, an attenuated RONS generation may facilitate IL-15 production, accompanied by STAT3 activation, in a process that does not require AMPK phosphorylation.

scholarly journals Effects of Oral Resveratrol Supplementation on Glycogen Replenishment and Mitochondria Biogenesis in Exercised Human Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3721
Author(s):  
Chun-Ching Huang ◽  
Chia-Chen Liu ◽  
Jung-Piao Tsao ◽  
Chin-Lin Hsu ◽  
I-Shiung Cheng
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Young Male ◽  
Gene Expressions ◽  
Plasma Parameters ◽  
Post Exercise ◽  
Glycogen Resynthesis ◽  
Mitochondria Biogenesis

The present study aimed to investigate the effect of oral resveratrol supplementation on the key molecular gene expressions involved in mitochondria biogenesis and glycogen resynthesis in human skeletal muscle. Nine young male athletes participated in the single-blind and crossover designed study. All subjects completed a 4-day resveratrol and placebo supplement in a randomized order while performing a single bout of cycling exercise. Immediately after the exercise challenge, the subjects consumed a carbohydrate (CHO) meal (2 g CHO/Kg body mass) with either resveratrol or placebo capsules. Biopsied muscle samples, blood samples and expired gas samples were obtained at 0 h and 3 h after exercise. The muscle samples were measured for gene transcription factor expression by real-time PCR for glucose uptake and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid concentrations and respiratory exchange ratio were analyzed during post-exercise recovery periods. The results showed that the muscle glycogen concentrations were higher at 3 h than at 0 h; however, there were no difference between resveratrol trial and placebo trial. There were no significantly different concentrations in plasma parameters between the two trials. Similarly, no measured gene expressions were significant between the two trials. The evidence concluded that the 4-day oral resveratrol supplementation did not improve post-exercise muscle glycogen resynthesis and related glucose uptake and mitochondrial biosynthesis gene expression in men.

scholarly journals Promoter-specific regulation of PPARGC1A gene expression in human skeletal muscle

2015 ◽  
Vol 55 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Daniil V Popov ◽  
Evgeny A Lysenko ◽  
Tatiana F Vepkhvadze ◽  
Nadia S Kurochkina ◽  
Pavel A Maknovskii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Stop Codon ◽  
Constitutive Expression ◽  
Alternative Promoter ◽  
Specific Expression ◽  
Post Exercise ◽  
Specific Regulation ◽  
Intensity Of Exercise

The goal of this study was to identify unknown transcription start sites of thePPARGC1A(PGC-1α) gene in human skeletal muscle and investigate the promoter-specific regulation ofPGC-1αgene expression in human skeletal muscle. Ten amateur endurance-trained athletes performed high- and low-intensity exercise sessions (70 min, 70% or 50%o2max). High-throughput RNA sequencing and exon–exon junction mapping were applied to analyse muscle samples obtained at rest and after exercise.PGC-1αpromoter-specific expression and activation of regulators of PGC-1α gene expression (AMPK, p38 MAPK, CaMKII, PKA and CREB1) after exercise were evaluated using qPCR and western blot. Our study has demonstrated that during post-exercise recovery, human skeletal muscle expresses thePGC-1αgene via two promoters only. As previously described, the additional exon 7a that contains a stop codon was found in all samples. Importantly, only minor levels of other splice site variants were found (and not in all samples). Constitutive expressionPGC-1αgene occurs via the canonical promoter, independent of exercise intensity and exercise-induced increase of AMPKThr172phosphorylation level. Expression ofPGC-1αgene via the alternative promoter is increased of two orders after exercise. This post-exercise expression is highly dependent on the intensity of exercise. There is an apparent association between expression via the alternative promoter and activation of CREB1.

Effect of short-term, high-intensity exercise training on human skeletal muscle citrate synthase maximal activity: single versus multiple bouts per session

2019 ◽  
Vol 44 (12) ◽  
pp. 1391-1394
Author(s):  
Martin J. MacInnis ◽  
Lauren E. Skelly ◽  
F. Elizabeth Godkin ◽  
Brian J. Martin ◽  
Thomas R. Tripp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Maximal Activity ◽  
High Intensity Exercise ◽  
Short Term ◽  
Significant Difference

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.

scholarly journals Menopause Delays the Typical Recovery of Pre-Exercise Hepcidin Levels after High-Intensity Interval Running Exercise in Endurance-Trained Women

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3866
Author(s):  
Víctor Alfaro-Magallanes ◽  
Pedro Benito ◽  
Beatriz Rael ◽  
Laura Barba-Moreno ◽  
Nuria Romero-Parra ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
High Intensity ◽  
Iron Homeostasis ◽  
Premenopausal Women ◽  
The Body ◽  
Peak Oxygen Consumption ◽  
Post Exercise ◽  
Running Exercise ◽  
Maximal Aerobic Speed ◽  
High Intensity Interval

Menopause commonly presents the gradual accumulation of iron in the body over the years, which is a risk factor for diseases such as cancer, osteoporosis, or cardiovascular diseases. Running exercise is known to acutely increase hepcidin levels, which reduces iron absorption and recycling. As this fact has not been studied in postmenopausal women, this study investigated the hepcidin response to running exercise in this population. Thirteen endurance-trained postmenopausal women (age: 51.5 ± 3.89 years; height: 161.8 ± 4.9 cm; body mass: 55.9 ± 3.6 kg; body fat: 24.7 ± 4.2%; peak oxygen consumption: 42.4 ± 4.0 mL·min−1·kg−1) performed a high-intensity interval running protocol, which consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed with 90-second recovery. Blood samples were collected pre-exercise, 0, 3, and 24 hours post-exercise. As expected, hepcidin exhibited higher values at 3 hours post-exercise (3.69 ± 3.38 nmol/L), but also at 24 hours post-exercise (3.25 ± 3.61 nmol/L), in comparison with pre-exercise (1.77 ± 1.74 nmol/L; p = 0.023 and p = 0.020, respectively) and 0 hour post-exercise (2.05 ± 2.00 nmol/L; p = 0.021 and p = 0.032, respectively) concentrations. These differences were preceded by a significant increment of interleukin-6 at 0 hour post-exercise (3.41 ± 1.60 pg/mL) compared to pre-exercise (1.65 ± 0.48 pg/m, p = 0.003), 3 hours (1.50 ± 0.00 pg/mL, p = 0.002) and 24 hours post-exercise (1.52 ± 0.07 pg/mL, p = 0.001). Hepcidin peaked at 3 hours post-exercise as the literature described for premenopausal women but does not seem to be fully recovered to pre-exercise levels within 24 hours post-exercise, as it would be expected. This suggests a slower recovery of basal hepcidin levels in postmenopausal women, suggesting interesting applications in order to modify iron homeostasis as appropriate, such as the prevention of iron accumulation or proper timing of iron supplementation.

High-intensity interval training increases SIRT1 activity in human skeletal muscle

2010 ◽  
Vol 35 (3) ◽  
pp. 350-357 ◽  
Author(s):  
Brendon J. Gurd ◽  
Christopher G.R. Perry ◽  
George J.F. Heigenhauser ◽  
Lawrence L. Spriet ◽  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Interval Training ◽  
Peak Oxygen Consumption ◽  
Peroxisome Proliferator ◽  
Mitochondrial Enzymes ◽  
High Intensity Interval Training ◽  
High Intensity Interval

The effects of training on silent mating-type information regulator 2 homolog 1 (SIRT1) activity and protein in relationship to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial content were determined in human skeletal muscle. Six weeks of high-intensity interval training (∼1 h of 10 × 4 min intervals at 90% peak oxygen consumption separated by 2 min rest, 3 days per week) increased maximal activities of mitochondrial enzymes in skeletal muscle by 28% to 36% (citrate synthase, β-hydroxyacyl-coenzyme A dehydrogenase, and cytochrome c oxidase subunit IV) and PGC-1α protein (16%) when measured 4 days after training. Interestingly, total muscle SIRT1 activity (31%) and activity per SIRT1 protein (58%) increased despite decreased SIRT1 protein (20%). The present data demonstrate that exercise-induced mitochondrial biogenesis is accompanied by elevated SIRT1 activity in human skeletal muscle.

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