Investigating metabolomic and phenotypic changes following exercise training and corresponding implications for cardiometabolic risk
The purpose of this dissertation was to study the effects of exercise training on the plasma metabolome and phenotypic changes in men and women with abdominal obesity, using both metabolomics and magnetic resonance imaging technologies. Our findings are based on data collected from a randomized controlled trial, wherein participants were assigned to a low amount low intensity, high amount low intensity, high amount high intensity, or control group. The objective of Study 1 was to examine plasma metabolome changes in response to chronic exercise and whether changes in metabolites are associated with change in cardiometabolic risk factors. While no significant differences between measured metabolites in the control and exercise arms were observed, we identified significant associations between changes in metabolite concentrations and improvements in cardiometabolic traits following exercise. These findings were based on the average group response; however, recent interest in personalized exercise medicine has prompted investigation of individual responses to exercise training. Given the epidemic of excess adiposity globally, characterizing the heterogeneity in adipose tissue (AT) response to exercise is clinically important. The objective of Study 2 was to characterize the magnitude and clinical relevance of individual responses for AT reduction following standardized exercise. We demonstrated that the probability of an individuals’ reduction in total and abdominal AT being clinically meaningful was greater than controls, independent of amount and/or intensity. The objective of Study 3 was to integrate our findings by assessing the influence of AT reduction on the plasma metabolome and subsequent changes in cardiometabolic risk following exercise. We found that exercise-induced reduction in visceral AT was independently associated with increases in pyroglutamic acid (linked to glutamate metabolism) and TCA cycle intermediates (succinic and fumaric acid). Taken together, our observations suggest that (1) alterations in metabolites are related to changes in cardiometabolic traits; (2) part of the relationship between metabolite changes and cardiometabolic traits may be explained by AT reduction following exercise; and (3) given that the magnitude of adiposity reduction is associated with identifiable plasma metabolites, it is possible blood-based measures can reflect a given individual’s AT response to exercise.