Peripheral Effects of Exercise on Cardiovascular Health (STRRIDE II)

BACKGROUND:

Substantial evidence supports a favorable relationship between cardiovascular fitness, physical activity, and cardiovascular health. In particular, it is well established that increased levels of physical activity result in favorable improvements in lipid and carbohydrate metabolism. There is also evidence that increased physical activity and cardiovascular fitness have beneficial effects on cardiovascular health, independent of the effects on specific cardiovascular risk factors. One hypothesis proposes that the beneficial effects of regular exercise in humans is mediated through peripheral mechanisms, in particular through the chronic adaptations in skeletal muscle to habitual exercise. The exercise exposure required to achieve health benefits is poorly defined and the mechanisms through which these beneficial adaptations occur are poorly understood. This study will investigate the peripheral biological mechanisms through which chronic physical activity alters carbohydrate metabolism and lipid metabolism, resulting in improvements in these parameters of cardiovascular health and fitness.

DESIGN NARRATIVE:

In Studies of a Targeted Risk Reduction Intervention through Defined Exercise II (STRRIDE II), participants will be randomly assigned to one of four exercise training regimens after a 4-month sedentary control period. After an initial ramp period of up to 2 months, participants will be asked to train for 6 months in a given exercise program. The programs differ either in the dose of aerobic exercise or in the mode (e.g., aerobic exercise, resistance exercise, or a combination). Parameters reflecting changes in carbohydrate and lipid metabolism will be studied at an integrative physiologic level and with measurable biological endpoints in peripheral skeletal muscle (capillary surface area). It is proposed that the elucidation of the peripheral mechanisms mediating the favorable responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better understanding of the health benefits conferred by physical activity and cardiovascular fitness. This may also point the way toward better exercise recommendations for clients with significant cardiovascular risk factors. The purpose of this study is to investigate the peripheral biological mechanisms through which chronic physical activity will alter carbohydrate metabolism and lipid metabolism that results in improvement in parameters of cardiovascular health and fitness. The driving hypothesis is that the health benefits derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. The mechanism of change in skeletal muscle differs by the mode of exercise training. It is hypothesized that the health benefits of aerobic exercise are mediated primarily by qualitative changes in skeletal muscles (alterations in exposed capillary surface area in skeletal muscle induced by exercise training) and that the health benefits of resistance exercise are mediated primarily by quantitative changes in skeletal muscles (alterations in fiber area in skeletal muscle induced by exercise training). The investigators will use combination exercise regimens in moderately obese patients with mild to moderate lipid metabolic abnormalities in order to investigate whether induced alterations in skeletal muscle fiber area, metabolic capacity, and capillary surface area account for favorable alterations in insulin sensitivity, glucose metabolism, lipoprotein levels, and lipid metabolism.