Exercise, neuropeptides and the hypothalamic regulation of appetite and energy balance
2014-05
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Exercise, neuropeptides and the hypothalamic regulation of appetite and energy balance
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2014-05
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This dissertation is focused on mechanisms involved in the central regulation of appetite, with particular focus on interventions affecting two specific hypothalamic nuclei involved in feeding and energy balance, the ventromedial hypothalamic (VMN) and paraventricular nuclei (PVN). The purpose of these investigations was to identify promising areas of intervention on brain mechanisms involved in the etiology of obesity. First I sought to determine whether exercise dynamically modifies the brain to promote negative energy balance via altering homeostatic appetitive responses. A thorough literature review was performed, which led to the conclusion that, particularly during obesity, aerobic exercise may promote negative energy balance via paradoxically reducing caloric intake despite the increased energy demands of exercise. I then performed a literature review to investigate one particular factor which I believe has promising relevance for how exercise may alter the structure or activity of appetitive regions in the hypothalamus, brain-derived neurotrophic factor (BDNF). In the hypothalamus, BDNF and its receptor, tropomyosin-related kinase B (trkB), are extensively expressed in areas associated with feeding and metabolism, and have been demonstrated to inhibit food intake and increase energy expenditure in both the PVN and VMN, leading to negative energy balance. Furthermore, BDNF via its receptor trkB has a known role in promoting synaptic plasticity and synaptogenesis. Since exercise has been shown to promote sustained alterations in appetite regulation toward maintenance of a leaner phenotype, I hypothesized that exercise-induced feeding reductions are associated with elevated BDNF and trkB in appetite related areas of the hypothalamus. Using Sprague-Dawley rats, I show that over an eight-week period cumulative food intake is reduced in exercising animals compared with sedentary controls, leading to an overall negative energy balance. I report that during the early stages of exercise training, PVN BDNF is elevated in relationship to the amount of running performed by the animals. I did not observe significant changes in BDNF at the eight-week time point, suggesting that exercise may result in early plasticity changes in the PVN, which may alter the function or responsiveness of the PVN during the long-term. In addition to BDNF, I measured trkB receptor in the PVN and surrounding area. I report discovery of trkB immunoreactive fibers surrounding the PVN that have not been previously described in the literature. Quantification of the density of trkB immunoreactive fibers in animals subjected to either volitional or forced running paradigms indicated that volitional running was associated with a reduction in fiber density compared with forced exercise. The second portion of this dissertation focuses on the effects of oxytocin in the VMN on energy balance. Oxytocin, specifically produced in the PVN, has been shown previously to be essential to maintaining energy balance. Currently, literature related to oxytocin is focused on either hindbrain effects of oxytocin on energy balance, or relies on intra cerebroventricular injections, which provide no information about potential sites of oxytocin forebrain effects. Using site-specific VMN injections, I demonstrate for the first time that oxytocin reduces feeding and increases both activity and energy expenditure in this forebrain site. These data are relevant to understanding mechanisms by which oxytocin reduces feeding, and provides insight into the role of oxytocin in the central regulation of energy balance.
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University of Minnesota Ph.D. dissertation. May 2014. Major: Nutrition. Advisors: Dr. ChuanFeng Wang and Dr. Catherine Kotz. 1 computer file (PDF); xi, 160 pages.
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Noble, Emily Elizabeth. (2014). Exercise, neuropeptides and the hypothalamic regulation of appetite and energy balance. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/163876.
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