Title page for ETD etd-08302010-202253

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
  • exercise
  • resistance training
  • melanocortin 3 receptor
  • melanocortin 1 receptor
  • inflammation
  • macrophage
  • monocyte
Date of Defense 2010-07-26
Availability unrestricted

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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