Substantial evidence supports a favorable relationships 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 exposures required to achieve health benefits in humans are poorly defined and the mechanisms through which there beneficial adaptations occur are poorly understood. The purpose of this study it to 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 in humans. The driving hypothesis is that health benefits derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle, probably related to alterations in exposed capillary surface area in skeletal muscle induced by exercise training. The strategy to be taken by the investigators to test the hypothesis is to use graded exercise regimens in moderately obese human subjects with mild to moderate lipid metabolic abnormalities to investigate whether induced alterations in skeletal muscle fiber type, metabolic capacity and capillary surface area account for favorable alterations in insulin sensitivity and glucose metabolism, lipoprotein levels and lipid metabolism. Specifically, subjects will be randomly assigned to one of three graded exercise training regimens or a sedentary control group and asked to train for six months at a given exercise intensity and dose. 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 (e.g., capillary surface area). A pilot study is already underway to identify problems with the study protocol and demonstrate feasibility of the study. 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 in humans and point the way toward better exercise recommendations for clients with significant cardiovascular risk factors.
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