If, like me, you sometimes need more motivation to exercise consistently—even though you know that it is good for you—you may be interested in the findings of a paper published recently in PLOS Genetics. The paper showed that consistent exercise over a 6-month period caused potentially beneficial changes in gene expression. In short, regular exercise caused expression of some “good” genes, and repression of “bad” ones, and these changes appeared to be controlled by epigenetic mechanisms.
Epigenetic changes are modifications to DNA that affect gene expression but don’t alter the underlying sequence. Perhaps the best understood example of an epigenetic change is DNA methylation—where methyl groups bind to the DNA at specific sites and alter expression, often by preventing transcription. Epigenetic changes have been shown to occur throughout all stages of development and in response to environmental factors such as diet, toxin exposure, or stress. The study of epigenetics is revealing more and more about how the information stored in our DNA is expressed in different tissues at different times and under different environmental circumstances.
The PLOS Genetics study suggests that regular aerobic exercise results in changes in methylation patterns that affect gene expression in adipose tissue. The exercise-induced changes affected expression of some genes that may be involved in fat storage and glucose metabolism. As part of the study, the authors used an Illumina Human Methylation BeadChip Kit to examine genome-wide DNA methylation patterns in adipose tissue samples from 23 healthy men over a 6-month period. Initially sedentary, the men participated in an exercise program involving up to 3 hours of aerobic activity per week. Global gene expression levels were assessed prior to starting the program and after 6 months of participation.
After 6 months of regular exercise, more than 17,500 sites in over 7,000 genes showed altered levels of DNA methylation (~16,000 sites showing increased methylation after exercise and 1,500 showing a decrease). The RALBP1 gene was one of the genes that showed increased DNA methylation and decreased mRNA expression after exercise. RALBP1 has been associated with metabolic syndrome (increased risk of heart disease and stroke). Using RALBP1 as an example, the authors were able to show that the increased DNA methylation at the RALBP1 promoter suppressed transcription of that gene. They then silenced two other genes that showed decreased methylation after exercise in adipocytes. Silencing of expression of these two genes resulted in increased lipogenesis, suggesting that decreased methylation of these genes may result in less fat storage.
At first glance this may seem like another one of these studies where molecular biology confirms something that we all knew anyway—exercise burns fat and reduces risk of diabetes and heart disease. However, the cool thing about this study (I think) is the elucidation of the mechanism of how this may work in terms of gene expression—in particular, the finding that changes in methylation pattern of genes in adipose tissue are induced as a result of exercise.
For me, this paper is a reminder of the key role that epigenetic studies are playing in helping us understand not only how genes are regulated, but also how environmental factors and lifestyle choices can influence these epigenetic events.
Here’s the paper:
Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH, Nilsson E, Tornberg A, Dekker Nitert M, Eriksson KF, Jones HA, Groop L, & Ling C (2013). A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue. PLoS genetics, 9 (6) PMID: 23825961
Isobel Maciver
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