Methylation is an epigenetic mechanism that can both positively and negatively regulate gene expression. Although methylation serves a critical role in driving many cell-specific and tissue- specific functions, it is now well-established that some, bu not all, epigenetic modifications of DNA may also occur in response to changes in the environment. Importantly, these changes can stably alter gene expression in a manner that may influence metabolism, behavior, and ultimately overall health. Exercise has been shown to have positive effects on both physical and mental health outcomes but the exact molecular mechanism driving stable changes in health following exercise are not well known. Our initial examination of methylation states before and after exercise training has provided evidence that methylation is labile to physiologic changes associated with exercise training, and that this liability may be a function of genomic background. We have performed extensive research characterizing over 3,000 individuals undergoing aerobic exercise training using a carefully-controlled and documented aerobic exercise regimen. We have collected multiple parameters related to exercise tolerance, including heart rate, intensity, duration, and total exercise exposure. In addition, we have both DNA and RNA from approximately 1,500 individuals, both pre- and post-exercise. In this project, we plan to characterize both whole genome methylation and gene expression in sedentary individuals'pre- and post-exercise training in order to identify the primary targets of alterations in gene regulation. This research has the potential to reveal new insights into the mechanisms that influence the ability to respond to or maintain health behaviors like physical activity.

Public Health Relevance

Though short-term weight loss can be achieved many ways, most current treatments for obesity have been largely unsuccessful in preventing weight re-gain. Many programs focus on behaviors such as diet and physical activity, with widely varied success among individuals. At least part of the variability that is seen in response to weight loss programs may be due to our genes. This project is designed to examine how genes act to influence the bodily functions and behaviors that control our body weight. A better understanding of how genes might influence both the ability to lose weight and to keep weight off will help to develop more effective programs to prevent or treat obesity.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-PSE-D (50))
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Karp, Robert W
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University of Texas Austin
Schools of Arts and Sciences
United States
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Bray, Molly S; Loos, Ruth J F; McCaffery, Jeanne M et al. (2016) NIH working group report-using genomic information to guide weight management: From universal to precision treatment. Obesity (Silver Spring) 24:14-22