What if you could change your body’s metabolism by just one visit to the gym? It is possible according to the latest study published in the Cell Metabolism (1) journal. The scientists examined biopsies of skeletal muscle obtained from sedentary participants before and after acute exercising. The pattern of their DNA methylation changed so that the genes responsible for cell metabolism were activated. The findings may surprise as it is generally thought that once the cell is mature, the pattern of DNA methylation is established. Here we find that the process is indeed dynamic and to some extent caffeine-related.
Environment induces DNA changes
What impacts the function of each tissue is the regulation of gene expression. As we know the genetic code is identical in all cells, but each cell type has its own gene expression pattern, which is propelled by a specific epigenetic signature. One of the major epigenetic modification is DNA methylation. It suppresses gene expression by changing the access of the transcription complex to the chromatin or by recruiting methyl binding proteins (2). DNA methylation is considered as mitotically stable. Therefore environmental factors are not expected to cause important and persistent changes in DNA methylation patterns in mature tissues. However, various studies do support the idea that in course of life environmentally induced shifts in DNA methylation model influence gene-expression signatures.
Unique tissue adjusts to physical exercise
Skeletal muscle can be characterized by a high plasticity in its adaptation to environmental stressors. The structural and metabolic capabilities of the tissue are then challenged. Physical exercise drives muscle contraction and provokes adaptive responses to improve the activity, metabolic efficiency and oxidative capacity. It happens through altering gene expression profiles and protein levels (3). It is unknown whether DNA methylation is in charge of these genomic responses. In the discussed study the evidence was provided that exercise-induced changes in gene expression is in fact associated with transient alterations in gene promoter methylation.
Cycling elevates gene expression
To determine the effect of exercise on DNA methylation, the scientists first analyzed global DNA methylation levels in biopsies of vastus lateralis skeletal muscle obtained from 14 healthy, young, sedentary men and women before and after an cycle ergometer exercise. Global methylation decreased after acute exercise, which means many genes were affected. Then the researchers evaluated the levels of various genes previously described to be of great metabolic significance and whose transcript is elevated after exercise (PGC-1α, TFAM, PPAR-, PDK4 and others). They found that the levels of methylated promoters for metabolic genes were lower after acute exercise, hence their expression was higher.
Gym season ticket rather than coffee
It has been found that aerobic exercise boosts gene transcription in a dose-dependent manner (4). Biopsies of skeletal muscle from a separate cohort of eight young healthy sedentary men were taken and confirmed this hypothesis. In addition scientists tested the mechanisms underlying gene promoters hypomethylation. Primary messengers such as changes in the AMP:ATP ratio, calcium release from the endoplasmic reticulum, or the intracellular redox state are thought to play a major role in response of muscle to exercise. Effects of caffeine help to understand the issue, as the substance seems to elevate the cytoplasmic Ca2+ levels and thus mimics exercise-induced expression of genes (5). Indeed, in this study it was found that caffeine causes promoter hypomethylation in rat myotubes. However, Juleen Zierath of the Karolinska Institute in Stockholm, a co-author of the described study, warns Nature (6) that “(to achieve the goal)one would need to consume a caffeine equivalent of about 50 cups per day, almost close to a lethal dose”.
1.Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle. Romain Barrès, Jie Yan, Brendan Egan et al. Cell Metabolism – 7 March 2012 (Vol. 15, Issue 3, pp. 405-411)
2.Linking DNA methylation and histone modification: patterns and paradigms. Cedar, H., and Bergman, Y. (2009)
Nat. Rev. Genet. 10, 295–304.
3.The molecular bases of training adaptation. Coffey, V.G., and Hawley, J.A. (2007) Sports Med. 37, 737–763.
4.Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle.
Egan, B., Carson, B.P., Garcia-Roves et al. J. Physiol. 588, 1779–1790.
5.Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle. Ojuka, E.O., Jones, T.E., Han, D.H. et al. FASEB J. 17, 675–681.
Want to know more exercises? Watch on medtube.net “Female Athlete Triad”