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Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Open accessAbstract
DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.
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“A review of available data suggests that tonic immobility, peritraumatic dissociation, and dissociative PTSD may be mediated by a shared neural network involving amygdala deactivation, absence of sympathetically mediated arousal symptoms (decreased skin conductance and an absence of heart rate increases), parasympathetic activation (a decrease in heart rate in some studies, presumably reflecting a”
From Fear and the Defense Cascade (2015) · cites this paper as [121]
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“The muscle contraction that occurs during exercise also causes intracellular perturbations that disturb metabolic homeostasis, thereby promoting a broad range of adaptive responses and increasing overall resilience in response to stress.157,158”
From Fear and the Defense Cascade (2015) · cites this paper as [157]
Citations
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“tion of the promoters of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferatoractivated receptor-delta (PPAR-δ) as well histone acetylation of glucose transporter 4 (GLUT4) and myocyte enhancer factor 2 (MEF2), have been shown…”
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Epigenetic Mechanisms of the Aging Human Retina
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“The transcription and translation processes are conjointly controlled by transcription factors,(3,4) histone modification,(5) and DNA methylation.(6,7) microRNAs (miRNAs) were first identified 20 years ago and have generated an additional level of complexity in our understanding of transcriptional and translational re…”
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BackgroundPhysical exercise and epigenetic modifications in skeletal muscle, brain, and heart
Zheng, X., Liu, X., Guo, Y., Lv, Y., Lin, C.-S., Wang, D., Wang, S., Liu, Y.-P., & Hu, X.-F. (2025) · Epigenetics & Chromatin · doi:10.1186/s13072-025-00576-8 · Cited by 37
“…that acute exercise induces hypomethylation of key metabolic gene promoters in human skeletal muscle, including per-oxisome proliferator-activated receptor-γ coactivator 1α ( PGC1α ), peroxisome proliferator-activated receptor-δ ( PPAR-δ ), and pyruvate dehydrogenase kinase 4 ( PDK4 ) [59].”
Humińska‐Lisowska, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111602 · Cited by 52
DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis
Parveen, N., & Dhawan, S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.651258 · Cited by 48
Physical exercise: An inducer of positive oxidative stress in skeletal muscle aging
Thirupathi, A., Pinho, R. A., & Chang, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117630 · Cited by 40
TET2 facilitates PPARγ agonist–mediated gene regulation and insulin sensitization in adipocytes
Bian, F., Ma, X., Villivalam, S. D., You, D., Choy, L. R., Paladugu, A., Fung, S., & Kang, S. (2018) · Metabolism · doi:10.1016/j.metabol.2018.08.006 · Cited by 38
“Extraordinary efforts have gone into defining the mechanisms that underlie insulin resistance, with most of the attention focused on insulin signal transduction and other mitochondrial and cytosolic pathways such as ER stress [1-5].”
BackgroundSynthesis, characterization and efficient photocatalytic activity of novel Ca/ZnO-Al2O3 nanomaterial
Elhalil, A., Elmoubarki, R., Farnane, M., Machrouhi, A., Mahjoubi, F., Sadiq, M., Qourzal, S., & Barka, N. (2018) · Materials Today Communications · doi:10.1016/j.mtcomm.2018.06.005 · Cited by 37
Boyne, D. J., O'Sullivan, D. E., Olij, B. F., King, W. D., Friedenreich, C. M., & Brenner, D. R. (2018) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-18-0175 · Cited by 45
“The study by Barres and colleagues (2012) observed a significant negative association between physical activity and global DNA methylation, which is in the opposite direction of the hypothesized effect (30).”
BackgroundSimulated microgravity attenuates myogenic differentiation via epigenetic regulations
Furukawa, T., Tanimoto, K., Fukazawa, T., Imura, T., Kawahara, Y., & Yuge, L. (2018) · npj Microgravity · doi:10.1038/s41526-018-0045-0 · Cited by 37
“interestingly reported that acute exercise tends to reduce global methylation on the entire genome, resulting in activation of regulated genes in human skeletal muscle.(26) Singh et al.”
Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study
da Silva, I. R. V., de Araújo, C. L. P., Dorneles, G. P., Peres, A., Bard, A. L., Reinaldo, G. P., Teixeira, P. J. Z., Lago, P. D., & Elsner, V. R. (2017) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2017.04.004 · Cited by 40
“The peripheral blood mononuclear cells (PBMCs) were isolated from EDTA blood through the density gradient technique as described by Bicalho et al. (1981).”
MethodThe metabolic vascular syndrome - guide to an individualized treatment
Hanefeld, M., Pistrosch, F., Bornstein, S. R., & Birkenfeld, A. L. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9345-4 · Cited by 44
“In addition to heritable regulation of the epigenome, there is also evidence of lifestyle-related modification of genes in adulthood [41].”
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Liang, R., Tang, Q., Chen, J., & Zhu, L. (2024) · Aging and Disease · doi:10.14336/ad.2024.1495 · Cited by 28
Effect of contractile activity on PGC-1α transcription in young and aged skeletal muscle
Carter, H. N., Pauly, M., Tryon, L. D., & Hood, D. A. (2018) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01110.2017 · Cited by 40
Effect of stress on human biology: Epigenetics, adaptation, inheritance, and social significance
Denhardt, D. T. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25837 · Cited by 76
“Barrès et al. (2012) found that exercise induced a dose-dependent expression of PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator, involved in mitochondrial function), PDK4 (pyruvate dehydrogenase kinase), and PPAR-δ (peroxisome proliferator-activated receptor-δ, associatedwith…”
BackgroundThe Destiny of Glucose from a MicroRNA Perspective
Mirra, P., Nigro, C., Prevenzano, I., Leone, A., Raciti, G. A., Formisano, P., Bèguinot, F., & Miele, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00046 · Cited by 40
“The methylation status and expression levels of PDK4 are also altered in T2D patients, but exercise is able to revert these effects (174).”
BackgroundGenome-wide analysis of DNA methylation patterns in horse
Lee, J.-R., Hong, C. P., Moon, J.-W., Jung, Y.-D., Kim, D., Kim, T., Gim, J., Bae, J., Choi, Y., Eo, J., et al. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-598 · Cited by 42
“Many previous studies suggested that exercise induces methylation changes [42,43], and athletic ability is closely associated with methylation [44,45].”
BackgroundThe therapeutic potential of exercise for neuropsychiatric diseases: A review
Swenson, S., Blum, K., McLaughlin, T., Gold, M. S., & Thanos, P. K. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116763 · Cited by 42
‘Exerkines’: A Comprehensive Term for the Factors Produced in Response to Exercise
Novelli, G., Calcaterra, G., Casciani, F., Pecorelli, S. L., & Mehta, J. L. (2024) · Biomedicines · doi:10.3390/biomedicines12091975 · Cited by 36
“Barres et al., shown that a long time that exercise alters epigenetics and causes short-term changes in DNA methylation and gene expression in muscle tissue that may have implications for type 2 diabetes [45].”
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“It is striking that <24 h of MYC induction can changemuscleDNAmethylation status, but a single bout of exercise also remodels DNA methylation in human muscle tissue (Barres et al., 2012; Maasar et al., 2021; Seaborne et al., 2018).”
BackgroundDifferentially methylated gene patterns between age‐matched sarcopenic and non‐sarcopenic women
He, L., Khanal, P., Morse, C. I., Williams, A. G., & Thomis, M. A. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12478 · Cited by 35
MacInnis, M. J., Skelly, L. E., & Gibala, M. J. (2019) · The Journal of Physiology · doi:10.1113/jp277633 · Cited by 41
“…exercise compared to work-matched low-intensity exercise, owing in part to the greater activation of activating transcription factor-2 (ATF-2) and histone deacetylase 4 (HDAC4) (Egan et al. 2010) and reduced methylation in the promoter regions of PGC1α and related genes (Barres et al. 2012).”
BackgroundRole of genetic and environmental factors in DNA methylation of lipid metabolism
He, Z., Zhang, R., Jiang, F., Hou, W., & Hu, C. (2017) · Genes & Diseases · doi:10.1016/j.gendis.2017.11.005 · Cited by 35
“An acute bout of exercise-induced hypomethylation of the PGC1a promoter region was observed in a dose-dependent manner along with a corresponding increase in mRNA expression levels in skeletal muscle.(37) Additionally, a study confirmed the effect of maternal exercise on PGC1a methylation in the skeletal muscle of mou…”
BackgroundHypermethylation: Causes and Consequences in Skeletal Muscle Myopathy
Majumder, A., Behera, J., Jeremić, N., & Tyagi, S. C. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25841 · Cited by 34
X chromosome-wide analysis identifies DNA methylation sites influenced by cigarette smoking
Klebaner, D., Huang, Y., Hui, Q., Taylor, J. Y., Goldberg, J. H., Vaccarino, V., & Sun, Y. V. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0189-2 · Cited by 33
“Specifically, epigenetic mechanisms may mediate environmental risks such as smoking [7–10], pollutants [11–13], and lifestyle behaviors [14–16] for chronic disease development.”
BackgroundNFκB2 Gene as a Novel Candidate that Epigenetically Responds to Interval Walking Training
Zhang, Y., Hashimoto, S., Fujii, C., Hida, S., Ito, K., Matsumura, T., Sakaizawa, T., Morikawa, M., Masuki, S., Nose, H., et al. (2015) · International Journal of Sports Medicine · doi:10.1055/s-0035-1547221 · Cited by 34
Hargreaves, M. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.006 · Cited by 32
DNA methylation of exercise-responsive genes differs between trained and untrained men
Geiger, C., Needhamsen, M., Emanuelsson, E. B., Norrbom, J., Steindorf, K., Sundberg, C. J., Reitzner, S. M., & Lindholm, M. E. (2024) · BMC Biology · doi:10.1186/s12915-024-01938-6 · Cited by 40
“Previous studies have shown exercise-induced demethylation of the proximal PGC-1α promoter as well as after long-term electrical stimulation in patients with spinal cord injuries [29, 56].”
BackgroundResultInfluentialDNA methylation in human diseases
Younesian, S., Mohammadi, M. H., Younesian, O., Momeny, M., Ghaffari, S. H., & Bashash, D. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e32366 · Cited by 48
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Epigenetic regulation of skeletal muscle metabolism
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“Also acute exercise affects the epigenome via promoter hypomethylation and increases the expression of PGC-1α, PDK4 and PPAR in skeletal muscle [85].”
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“3 mM palmitate, and 4% fatty acid-free BSA and incubated for 30 min (3).”
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“, 2011) and, inter alia, mitochondrial biogenesis (Barrès et al., 2012), we aimed to investigate the distribution of the MTHFR 1298A>C polymorphism in two independent Polish and Russian casecontrol studies, where athletes were categorised into one of the four groups, according to the energy requirements of their disci…”
BackgroundInfluentialTour de France Champions born or made: where do we take the genetics of performance?
Moran, C. N., & Pitsiladis, Y. P. (2017) · Journal of Sports Sciences · doi:10.1080/02640414.2016.1215494 · Cited by 32
“Like genetic variants, epigenetic modifications are heritable (Rissman & Adli, 2014); however, unlike genetic variants, they are also malleable within an individual (Baggish et al., 2011; Barrès et al., 2012).”
BackgroundHypoxia and aging: molecular mechanisms, diseases, and therapeutic targets
Nisar, A., Khan, S., Li, W., Hu, L., Samarawickrama, P. N., Gold, N. M., Zi, M., Mehmood, S. A., Miao, J., & He, Y. (2024) · MedComm · doi:10.1002/mco2.786 · Cited by 33
“Physical activity has been shown to remodel DNA methylation patterns on the promoters of key genes in skeletal muscle, 278 and histone modifications may also be affected through the inhibition of HDACs, thus altering gene expression profiles.”
BackgroundAbraham, M. J., Elsherbini, A., El-Diasty, M., Askari, S., & Szewczuk, M. (2023) · Biomolecules · doi:10.3390/biom13020318 · Cited by 31
“[75] found a decrease in global DNA methylation after an acute bout of exercise.”
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“Current dogma indicates that decreased methylation (hypomethylation) of CpG sites, particularly if occurring in promoter regions, contributes to increased gene expression whereas increased methylation (hypermethylation) contributes to gene silencing [19,21].”
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“In skeletal muscle in vivo, a similar reduction in promoter methylation of the PGC-1α gene was associated with elevated transcription [12].”
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“Exercise can modify DNA methylation profiles to control glucose metabolism, recovery, and dissimilation of lactate (Barres et al., 2012).”
InfluentialRomagnolo, D. F., Zempleni, J., & Selmin, O. I. (2014) · Advances in Nutrition · doi:10.3945/an.114.005868 · Cited by 36
“Conversely, exercise induces acute expression of PGC-1a, PDK4, and PPARd in skeletal muscle via reduced CpG methylation of the respective promoters (98).”
BackgroundThe Epigenome and Its Role in Diabetes
Waki, H., Yamauchi, T., & Kadowaki, T. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0328-x · Cited by 31
Human skeletal muscle possesses an epigenetic memory of high intensity interval training
Pilotto, A., Turner, D., Mazzolari, R., Crea, E., Brocca, L., Pellegrino, M., Miotti, D., Bottinelli, R., Sharples, A., & Porcelli, S. (2024) · bioRxiv · doi:10.1101/2024.05.30.596458 · Cited by 30
“Secondly, the exercise paradigm used by Lindholm et al., (2016) included moderate intensity activities while DNA methylation and gene expression involved in targeted metabolic and oxidative pathways seem to be more affected by high intensity aerobic exercise (Barrès et al., 2012).”
BackgroundMethodCosta, G. A., Silva, N. K. D. G. T., Marianno, P., Chivers, P., Bailey, A., & Camarini, R. (2023) · Neuroscience · doi:10.2139/ssrn.4265447 · Cited by 30
“Methylation status of Bdnf exon IV CpG islands are stretches that have a higher CG density compared with other genome regions which are generally not methylated (Bird et al., 1985).”
BackgroundKlasić, M., Markulin, D., Vojta, A., Samaržija, I., Biruš, I., Dobrinić, P., Ventham, N. T., Trbojević‐Akmačić, I., Šimurina, M., Štambuk, J., et al. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0507-y · Cited by 41
Mudry, J. M., Lassiter, D. G., Nylén, C., García-Calzón, S., Näslund, E. B., Krook, A., & Zierath, J. R. (2016) · Diabetes · doi:10.2337/db16-0882 · Cited by 32
“DNA methylation in skeletal muscle are also triggered by exercise (20-22), dietary factors”
BackgroundSelf-citationThe integration of epigenetics and genetics in nutrition research for CVD risk factors
Ma, Y., & Ordovás, J. M. (2016) · Proceedings of The Nutrition Society · doi:10.1017/s0029665116000823 · Cited by 34
Solagna, F., Nogara, L., Dyar, K. A., Greulich, F., Mir, A. A., Türk, C., Bock, T., Geremia, A., Baraldo, M., Sartori, R., et al. (2020) · Acta Physiologica · doi:10.1111/apha.13496 · Cited by 35
“23 Other studies looked at histone modifications after exercise, without clearly linking it to the induction of specific genes.”
Hierarchical framework to improve individualised exercise prescription in adults: a critical review
Lehtonen, E., Gagnon, D. D., Eklund, D., Kaseva, K., & Peltonen, J. E. (2022) · BMJ Open Sport & Exercise Medicine · doi:10.1136/bmjsem-2022-001339 · Cited by 36
Chen, X., Lin, Q., Wen, J., Lin, W., Liang, J., Huang, H., Li, L., Huang, J., Chen, F., Liu, D., et al. (2019) · Journal of Diabetes Investigation · doi:10.1111/jdi.13201 · Cited by 32
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“Moreover, previous investigations have shown that methylome-wide changes related to metabolic disease have potential for modification.(35) Given the overlap we have observed between AATD-related and obesity-related liver disease, similar strategies in AATD may be fertile ground for future research.”
ResultKasch, J., Kanzleiter, I., Saussenthaler, S., Schürmann, A., Keijer, J., van Schothorst, E. M., Klaus, S., & Schumann, S. (2018) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2018.03.015 · Cited by 30
Epigenetic modulation of metabolic decisions
Öst, A., & Pospisilik, J. A. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.005 · Cited by 28
Genes and power athlete status
Maciejewska, A., Sawczuk, M., Cięszczyk, P., & Ahmetov, I. I. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816193-7.00003-8 · Cited by 26
Sun, Y. V. (2014) · Current Genetic Medicine Reports · doi:10.1007/s40142-014-0058-2 · Cited by 27
“In light of recent MWAS findings of physical activity [48•], [49], BMI [15••] and blood lipids [16], we will be able to examine the predictive ability of the MRS and may improve the prognosis of chronic diseases.”
Li, A., Yau, S.-Y., Machado, S., Wang, P., Yuan, T.-F., & So, K.-F. (2019) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527318666190308102804 · Cited by 27
Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus
Mannar, V., Boro, H., Patel, D., Agstam, S., Dalvi, M., & Bundela, V. (2023) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2023.19.1.46 · Cited by 38
“Review Diabetes touchREVIEWS in Endocrinology muscles of subjects with T2DM.35 Further human and animal studies of skeletal muscle suggested methylation defects in genes that regulate insulin sensitivity, such as NDUFB6,36 COX5a,37 OXPHOS,38 PGC- 1α,39 PDK4 and PPAR-δ.40 Studies in rats with obesity induced by a high-…”
BackgroundInfluentialExercise training enhances muscle mitochondrial metabolism in diet-resistant obesity
Pileggi, C. A., Blondin, D. P., Hooks, B. G., Parmar, G., Alecu, I., Patten, D. A., Cuillerier, A., O’Dwyer, C., Thrush, A. B., Fullerton, M. D., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104192 · Cited by 37
Epigenetic Responses to Acute Resistance Exercise in Trained vs. Sedentary Men
Bagley, J. R., Burghardt, K. J., McManus, R. T., Howlett, B. H., Costa, P. B., Coburn, J. W., Arevalo, J. A., Malek, M. H., & Galpin, A. J. (2019) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003185 · Cited by 34
“By contrast, Barrès et al (3) used a luminometric methylation assay and found a decrease in global methylation 20 minutes after acute aerobic exercise in sedentary individuals.”
BackgroundResultInfluentialLund, J., Helle, S. A., Li, Y., Løvsletten, N. G., Stadheim, H. K., Jensen, J., Kase, E. T., Thoresen, G. H., & Rustan, A. C. (2018) · Scientific Reports · doi:10.1038/s41598-018-35715-7 · Cited by 31
Impact of nutrition on pollutant toxicity: an update with new insights into epigenetic regulation
Hoffman, J. B., Petriello, M. C., & Hennig, B. (2017) · Reviews on Environmental Health · doi:10.1515/reveh-2016-0041 · Cited by 30
“For example, one study found that acute exercise resulted in changes in the methylation of the promoter region of genes involved in energy and glucose homeostasis, including pyruvate dehydrogenase kinase isoenzyme 4 (PDK4), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1α), and peroxisome pr…”
Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation
Furukawa, R., Hachiya, T., Ohmomo, H., Shiwa, Y., Ono, K., Suzuki, S., Satoh, M., Hitomi, J., Sobue, K., & Shimizu, A. (2016) · Scientific Reports · doi:10.1038/srep26424 · Cited by 30
Pérez‐Schindler, J., & Philp, A. (2015) · Clinical Science · doi:10.1042/cs20150246 · Cited by 28
Chambers, T. L., Dimet‐Wiley, A., Keeble, A. R., Haghani, A., Lo, W., Kang, G., Brooke, R. T., Horvath, S., Fry, C. S., Watowich, S. J., et al. (2024) · The Journal of Physiology · doi:10.1113/jp286681 · Cited by 30
“It is generally considered that promoter and first exon hypomethylation relates to positive regulation of gene expression (Brenet et al., 2011; Feinberg & Vogelstein, 1983), as was first reported in skeletal muscle for PGC1 α (Barrès et al., 2012).”
Epigenetic and “redoxogenetic” adaptation to physical exercise
Radak, Z. O., Pan, L., Zhou, L., Mozaffaritabar, S., Gu, Y., Pinho, R. A., Zheng, X., Ba, X., & Boldogh, I. R. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.11.005 · Cited by 31
Santos, J. L., Krause, B. J., Cataldo, L. R., Vega, J. A., Salas‐Pérez, F., Mennickent, P., Gallegos, R., Milagro, F. I., Prieto-Hontoria, P. L., Riezu‐Boj, J. I., et al. (2020) · Nutrients · doi:10.3390/nu12092790 · Cited by 29
“Interestingly, it was also reported that the exercise-induced hypomethylation of PPARGC1A promoter is accompanied by an increased gene expression in skeletal muscle [18].”
BackgroundAlKhatib, A. H., & Tuomilehto, J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64358-1 · Cited by 19
Epigenetic effects of physical activity in elderly patients with cardiovascular disease
Recchioni, R., Marcheselli, F., Antonicelli, R., Mensà, E., Lazzarini, R., Procopio, A., & Olivieri, F. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.016 · Cited by 26
“…hypothesized that epigenetic mechanisms, such as histone post-translational modifications (hPTMs) (McGee and Hargreaves, 2011), DNA methylation (Barrès et al., 2012) and cellular microRNA (miRNA, miR) expression profiles (Denham and Prestes, 2016) and circulating miRNA signatures (de…”
BackgroundDevarshi, P. P., Jones, A., Taylor, E. M., Stefañska, B., & Henagan, T. M. (2017) · PPAR Research · doi:10.1155/2017/3235693 · Cited by 28
“Exercise training, dietary fat content, long chain fatty acid exposure, and the presence of diabetes and overweight or obesity have all been shown to epigenetically regulate Pgc-1α mRNA expression and downstream mitochondrial adaptations in skeletal muscle [5, 6, 13, 15, 16].”
BackgroundLiving long and ageing well: is epigenomics the missing link between nature and nurture?
The ACUME2 Project, Rea, I. M., Dellett, M., & Mills, K. (2015) · Biogerontology · doi:10.1007/s10522-015-9589-5 · Cited by 29
“Intriguingly, methylation was also reduced after a cup of coffee and although this did not mimic the methylation effect of exercise, in a series of elegant 'in vitro' experiments Barrès et al. (2012) suggested that calcium flux from mitochondria was likely involved.”
BackgroundHenagan, T. M. (2014) · Journal of Nutritional Health & Food Science · doi:10.15226/jnhfs.2014.00127 · Cited by 24
“Exercise training has also been shown to alter epigenetic modifications in association with insulin sensitivity and improvements in adiposity and mitochondrial function [28].”
BackgroundMeldi, K. M., Gaconnet, G., & Mayo, K. E. (2012) · Endocrinology · doi:10.1210/en.2012-1292 · Cited by 28
Precision Medicine in Obesity and Type 2 Diabetes: The Relevance of Early-Life Exposures
Estampador, A. C., & Franks, P. W. (2017) · Clinical Chemistry · doi:10.1373/clinchem.2017.273540 · Cited by 32
Unraveling precision exercise: A journey from efficacy to molecular insights
Nasb, M., Wei, M., Lin, B., & Chen, N. (2024) · Advanced Exercise and Health Science · doi:10.1016/j.aehs.2024.01.004 · Cited by 34
Rigalli, J. P., Theile, D., Nilles, J., & Weiß, J. (2021) · Cells · doi:10.3390/cells10113137 · Cited by 24
Tomiga, Y., Sakai, K., Ra, S., Kusano, M., Ito, A., Uehara, Y., Takahashi, H., Kawanaka, K., Soejima, H., & Higaki, Y. (2021) · The FASEB Journal · doi:10.1096/fj.202100630r · Cited by 37
Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review
Andrade, S., Morais, T., Sandovici, I., Seabra, A. L., Constância, M., & Monteiro, M. P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.681649 · Cited by 29
“Moreover , PPARGC1A methylation was shown to be highly responsive to exercise (45) and bariatric surgery (42).”
BackgroundMetabolic effects of physiological levels of caffeine in myotubes
Schnuck, J., Gould, L. M., Parry, H. A., Johnson, M. A., Gannon, N. P., Sunderland, K., & Vaughan, R. (2017) · Journal of physiology and biochemistry · doi:10.1007/s13105-017-0601-1 · Cited by 25
Nguyen, A. Q., Duquette, N., Mamarbachi, M., & Thorin, É. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151526 · Cited by 29
“Albeit this cannot be dismissed, a previous study in human skeletal muscle showed that acute exercise induces transient changes in the methylation of genes with changes in expression only observed later, once methylation changes reverted to pre-exercise levels [69].”
BackgroundInfluence of tissue, age, and environmental quality on DNA methylation in Alligator mississippiensis
Parrott, B. B., Bowden, J. A., Kohno, S., McCoy, J. A., Hale, M. D., Bangma, J., Rainwater, T. R., Wilkinson, P. M., Kucklick, J. R., & Guillette, L. J. (2014) · Reproduction · doi:10.1530/rep-13-0498 · Cited by 26
“For example, global hypomethylation of genomic DNA was observed in skeletal muscle in men and women shortly after exercise (Barrès et al. 2012).”
BackgroundTechniques of DNA Methylation Analysis with Nutritional Applications
Mansego, M., Milagro, F., Campión, J., & Martinez, J. (2013) · Lifestyle Genomics · doi:10.1159/000350749 · Cited by 25
An Overview of the Molecular Basis of Epigenetics
Sweatt, J. D., Nestler, E. J., Meaney, M. J., & Akbarian, S. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-391494-1.00001-x · Cited by 41
A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons
Moissidis, M., Abbasova, L., Selten, M. M., Alis, R., Bernard, C., Domínguez-Canterla, Y., Oozeer, F., Qin, S., Kelly, A., Mòdol, L., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.029 · Cited by 38
Genetic Determinants of Endurance: A Narrative Review on Elite Athlete Status and Performance
Bicakci, B., Cięszczyk, P., & Humińska‐Lisowska, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313041 · Cited by 36
The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth
Edman, S., Jones, R. G., Jannig, P. R., Fernandez‐Gonzalo, R., Norrbom, J., Thomas, N. T., Khadgi, S., Koopmans, P. J., da Silva, F. M., Chambers, T. L., et al. (2024) · EMBO Reports · doi:10.1038/s44319-024-00299-z · Cited by 44
“This result seems intuitive since changes in DNA methylation typically precede changes in gene expression (Barres et al, 2012), which does not peak until later time points in our data.”
Hjort, L., Novakovic, B., Cvitic, S., Saffery, R., Damm, P., & Desoyé, G. (2022) · Epigenetics · doi:10.1080/15592294.2022.2111755 · Cited by 28
“Indeed, in multiple studies PGC1A DNAm was directly associated with PGC1A mRNA expression and increased PGC1A promoter DNAm is positively associated with T2DM and physical inactivity [42,43].”
BackgroundBenrick, A., Pillon, N. J., Nilsson, E., Lindgren, E., Krook, A., Ling, C., & Stener‐Victorin, E. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa165 · Cited by 26
“Exercise positively remodels transcriptional and epigenetic profiles in skeletal muscle (45, 46), but whether electroacupuncture-induced contractions can induce similar benefits is unclear.”
BackgroundSelf-citationEpigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention
Park, H. L. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17041181 · Cited by 39
Impact of parental exercise on epigenetic modifications inherited by offspring: A systematic review
Axsom, J., & Libonati, J. R. (2019) · Physiological Reports · doi:10.14814/phy2.14287 · Cited by 37
“, Pgc-1 alpha, PDK4, and PPAR delta) was observed after completing a single-session of cycling at 80% of VO2peak (Barres et al., 2012).”
BackgroundMethodDaniele, S., Costa, B., Pietrobono, D., Giacomelli, C., Iofrida, C., Trincavelli, M. L., Fusi, J., Franzoni, F., & Martini, C. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/3740345 · Cited by 22
“Moreover, the gene for neurotrophic factor BDNF (brain-derived growth factor) is known to be remodelled epigenetically in the hippocampus in response to physical exercise [13].”
Background
Metadata
- Authors
- Barrès, R., Yan, J., Egan, B., Treebak, J. T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D. J., & Zierath, J. R.
- Affiliations
- University of Copenhagen (DK)
- Karolinska University Hospital (SE)
- Corresponding author
- Zierath, Juleen R.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 15
- Issue
- 3
- Pages
- 405-411
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2113728034
- Cited by
- 965
- References
- 32
- Citations by year
- 2026: 65 · 2025: 64 · 2024: 61 · 2023: 39 · 2022: 67 · 2021: 73 · 2020: 53 · 2019: 67 · 2018: 75 · 2017: 79 · 2016: 65 · 2015: 77 · 2014: 76 · 2013: 75 · 2012: 28
- FWCI
- 32.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, promoter hypomethylation, acute exercise, skeletal muscle, PGC-1α, PDK4, PPARδ, gene expression regulation, muscle contraction, caffeine, soleus muscle, L6 myotubes, epigenetic regulation
- MeSH terms
- Adult, Animals, Female, Humans, Male, Mice, Inbred C57BL, Exercise, Muscle, Skeletal, DNA Methylation, Mice, Young Adult
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