CNS and peripheral mechanisms by which voluntary running wheel exercise affects adiposity and glucose metabolism
Year: 2011
Type: article
Abstract: The worldwide increase in the prevalence of obesity and its co-morbidities, such as Type 2 Diabetes (T2D), cardiovascular disease and stroke, has heightened the urgency for the discovery of effective therapies.Increased physical activity and exercise reduce adiposity and risk of comorbidities.In order to maintain energy balance and defend body weight, signals from the periphery are integrated in the brain to result in shifts in feeding behavior and energy expenditure.However, when a decrease in stored fat occurs 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 amount of adiposity .Moreover, the CNS mechanisms by which exercise prevents or reduces diet-induced obesity (DIO) are still 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.Additionally, 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 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 the arcuate (ARC) and ventromedial hypothalamic (VMH) nuclei 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, thus exerting a negative feedback on the !$! expansion of fat mass.However, diets rich in fats 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 calorie restriction in order to match the body weight and fat to those of exercised mice, resulted in a 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 calorie restriction as interventions to achieve prevention of HFD-induced weight and fat gain, we find that exercise preserves leptininduced neuronal activation in the ARC and VMH, while calorie restriction prevents HFDinduced leptin resistance only in the ARC.Since the ARC and VMH play pivotal roles in the control of energy homeostasis, 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 exerciseinduced central effects, strongly supporting exercise as an intervention strategy for the prevention and treatment of obesity and related impaired glucose homeostasis.opportunity to feel the sense of accomplishment that came from working in the fields.If it were not for that, I likely would have little drive for nitty gritty of science.Thank you Katie and Jerome for your support from afar, I love you and miss you.Gracias a mis suegros, Mario y Dina, y a mi cuñada, Karina, por ser mi familia, por darme alegria, y por escuchar a mis intentos de explicar esta tesis en castellano.Gracias por ayudarme en los trabajos cotidianos, su ayuda me permiti a continuar.Su paciencia me ha ayudado mucho.Lastly, thank you to my husband, Paul.Aside from my training, I believe that Cincinnati's purpose in my life was to have me meet you.Thank you for your support throughout this whole process.It would have been so easy for me to forget about life outside of science if it weren't for you.Thank you for bringing me balance.It is only with your unwavering support, patience and love, that I have been able to accomplish this.You have lifted me when I have fallen, and forced me to acknowledge my accomplishments.Thank you for believing in me.I love you.!)! !!!!!"In order for man to succeed in life, God provided him with two means: education and physical activity.Not separately, one for the soul and the other for the body, but for the two together.With these two means, man can attain perfection."
Authors: Krawczewski Carhuatanta, Kimberly A. Mallett
Institution: University of Cincinnati
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W118718156