Type of Document	Dissertation
Author	Henagan, Tara Michelle
URN	etd-08302010-202253
Title	Exercise-Induced Alterations in Melanocortin Receptor Expression and Inflammation
Degree	Doctor of Philosophy (Ph.D.)
Department	Kinesiology
Advisory Committee	Advisor Name Title Stewart, Laura K. Committee Chair McLaughlin, Leslie D. Committee Member Nelson, Arnold G. Committee Member Welsch, Michael Committee Member Keenan, Michael J. Dean's Representative
Keywords	exercise resistance training melanocortin 3 receptor melanocortin 1 receptor inflammation macrophage monocyte
Date of Defense	2010-07-26
Availability	unrestricted
Abstract Inflammatory cytokines play a significant role in the pathogenesis of obesity-related diseases and have been implicated as integral factors in both early and late phases of atherosclerosis. Lifestyle modifications such as increasing physical activity and making dietary changes to induce weight loss are part of the primary prescription for the treatment of metabolic syndrome. Additionally, physical activity has been implicated as a potentially effective regimen for the control of inflammation, yet little is known about the anti-inflammatory mechanistic alterations induced by physical activity. Exercise training causes acute changes in inflammation immediately post exercise, evidenced by upregulation of inflammatory cytokines and increased activity of leukocytes. Production of inflammatory cytokines leads to increased circulating levels of monocytes and macrophages as well as other immune cells. Additionally, chronic changes in inflammation occur after recurring bouts of exercise, evidenced by upregulation and production of anti-inflammatory cytokines and increased sensitivity of macrophages to stimuli. Previous publications from our laboratory have found that whole blood samples from exercise trained individuals possess significantly increased sensitivity to lipopolysaccharide (LPS) stimuli, resulting in lower levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis alpha (TNFα). Others have also noted the decrease in circulating levels of inflammatory cytokines chronically with exercise training. The research presented in this dissertation is novel in that it explores the expression of the melanocortin receptors (MCR) on the plasma membranes of systemic monocytes, indicating a novel role for the MCRs as anti-inflammatory receptors that are regulated by chronic exercise training. The melanocortin 1 receptor (MC1R) and melanocortin 3 receptor (MC3R) are expressed on immune cell populations. Several lines of in vitro research have shown that activation of the MC3R on cultured macrophages leads to pregulation of the anti-inflammatory pathways, suggesting a novel role for MCRs in mediating exercise-induced inflammation. Here, I show that 12 weeks of resistance training in a young, healthy population decreases both MC1R and MC3R receptor density on systemic monocytes in conjunction with decreases in C-reactive protein (CRP). Furthermore, the percentage of circulating monocytes expressing MC1R increases whiles those expressing MC3R decreases in response to resistance training.
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