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CNS and peripheral mechanisms by which voluntary running wheel exercise affects adiposity and glucose metabolism

Krawczewski Carhuatanta, Kimberly A.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1320326553

Abstract Details

2011, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
The worldwide increase in the prevalence of obesity and its co-morbidities, such as Type 2 Diabetes (T2D), has heightened the urgency for the discovery of effective therapies. Increased physical activity and exercise reduce adiposity and risk of co-morbidities. Peripheral signals are integrated in the brain to maintain energy balance and defend body weight, controlling feeding behavior and energy expenditure. However, when fat stores decrease due to exercise, the increased energy expenditure during exercise is not necessarily accompanied by compensatory changes in resting energy expenditure or feeding. Therefore, we hypothesize that exercise acts on neuronal circuits involved in the control of energy balance to lower the defended fat store. Moreover, CNS mechanisms by which exercise prevents or reduces diet-induced obesity (DIO) remain unknown. Here, we show that voluntary exercise promotes leanness via increased energy expenditure, and prevents the obesigenic effects of high-fat diet (HFD), greatly attenuating fat mass gain. Additionally, exercised animals display improvements in their metabolic profile and glucose metabolism. We tested the hypothesis that exercise improves insulin sensitivity and glucose metabolism in mice fed HFD independent of its body weight effects. We found that prevention of HFD-induced weight and fat gain by both exercise and calorie restriction (CR) improves glucose tolerance despite having little effect in attenuating HFD-induced insulin resistance. Using a marker for chronic neuronal activation, we identify novel neural circuits involved in the beneficial effects of exercise. We show that exercise induces plastic changes in arcuate (ARC) and ventromedial hypothalamic (VMH) neurons as well as increasing chronic neuronal activation in leptin-receptor positive neurons in the VMH, whereas HFD decreases it. Leptin is a peripheral signal, released from fat that acts in the hypothalamus to curb appetite and increase energy expenditure when fat stores increase, exerting a negative feedback on the expansion of fat mass. However, HFD and a sedentary lifestyle can cause obesity and leptin resistance. In our experiments, the use of voluntary wheel running (VRW) prevents DIO and preserves the anorectic and weight-reduction effects of leptin. The prevention of DIO in sedentary mice using CR to match the body weight and fat to exercised mice, resulted in partial preservation of the anorexic effect of leptin, indicating that weight regulation by exercise can improve CNS leptin action independent of the effects of exercise on body weight reduction. Using exercise and CR to prevent HFD-induced weight and fat gain, we find that exercise preserves leptin-induced neuronal activation in the ARC and VMH, while CR prevents HFD-induced leptin resistance only in the ARC. Since the ARC and VMH play pivotal roles in the energy homeostasis control, the preservation of leptin action in these areas could be essential to maintain lower adiposity during consumption of HFD. Future studies will determine whether improved central leptin action in these nuclei is required for the beneficial effects of exercise on body composition. Thus, our findings provide overwhelming support for beneficial exercise-induced central effects, supporting exercise as an intervention strategy for the prevention and treatment of obesity and related impaired glucose homeostasis.
Silvana Obici, MD (Committee Chair)
Stephen Benoit, PhD (Committee Member)
James Herman, PhD (Committee Member)
Randall Sakai, PhD (Committee Member)
Darleen Sandoval, PhD (Committee Member)
Stephen Woods, PhD (Committee Member)
155 p.
Neurology
exercise; leptin; diet induced obesity; HFD; glucose metabolism

Recommended Citations

Citations

  • Krawczewski Carhuatanta, K. A. (2011). CNS and peripheral mechanisms by which voluntary running wheel exercise affects adiposity and glucose metabolism [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1320326553

    APA Style (7th edition)

  • Krawczewski Carhuatanta, Kimberly. CNS and peripheral mechanisms by which voluntary running wheel exercise affects adiposity and glucose metabolism. 2011. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1320326553.

    MLA Style (8th edition)

  • Krawczewski Carhuatanta, Kimberly. "CNS and peripheral mechanisms by which voluntary running wheel exercise affects adiposity and glucose metabolism." Doctoral dissertation, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1320326553

    Chicago Manual of Style (17th edition)

ucin1320326553
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© 2011, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.