EXERCISE INDUCED BIOCHEMICAL AND ANATOMICAL ADAPTATIONS

Washington University, Saint Louis MO

Investigators

Linked publications, trials & patents

Abstract

? DESCRIPTION (provided by applicant): Exercise deficiency is a major public health problem in the U.S. It is a major contributor to the development of obesity, type 2 diabetes, ischemic heart disease and of frailty in old age. The purpose of this research project is to determine and elucidate the mechanisms that mediate the adaptive responses of skeletal muscle to endurance exercise. These adaptations include an increase in mitochondrial biogenesis that results in increases in the capacity for substrate oxidation, and in exercise capacity and endurance. They also include an increase in the insulin-responsive glucose transporter GLUT4. Because these adaptations play key roles in mediating the beneficial effects of exercise on health and functional capacity much of our research is focused on the regulation of mitochondrial biogenesis and GLUT4 expression. A large segment of the population in the USA does not exercise regularly, and most people cannot be motivated to exercise regularly long-term. We have, therefore, become interested in discovering an exercise mimetic that could provide some of the health benefits of exercise. We have found that overexpression of PPARß in muscle results in adaptations that mimic the adaptive response to exercise. One component of our proposed research is to evaluate pharmacological activation of PPAR? as an exercise mimetic. Endurance exercise results in rapid activation and increased expression of PGC-1?. We think that this is the mechanism by which exercise induces an increase in mitochondrial biogenesis. However a number of investigators have reported that PGC-1? is not necessary for the exercise-induced increase in mitochondria. We propose an experiment to resolve this controversy as a component of this project.