This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity related metabolic disorders, such as insulin resistance, are a major health problem. If untreated, many obese individuals will develop Type 2 diabetes, of which insulin resistance is a primary symptom. Obese individuals have excessive availability of fat in their blood and uptake by the skeletal muscle, which has been causally linked with the development of insulin resistance. For example when the availability of fat in the blood is increased in lean, healthy people to levels similar to those found in obesity, insulin resistance occurs. A single session of exercise increases insulin sensitivity for hours to days after exercise, and this effect is preserved in obesity, although the mechanisms are not completely understood. To date no study has investigated the effect of exercise on the fat-induced reduction in insulin sensitivity. To do this we will examine insulin sensitivity during a fat infusion in lean (body mass index < 25 kg/m2), healthy females (18-45 yrs), the morning after subjects have either remained sedentary or performed a single session of exercise. Also, we will assess how a single session of exercise affects the storage and oxidation of fat within the muscle as well as the expression of genes and proteins involved in fat metabolism. Subjects will perform both trials in a randomized order. We hypothesize that exercise will be able prevent insulin resistance that is caused by increased fat availability and that this prevention will occur in parallel with changes in the ability to store and oxidize fat within the muscle. Determining the effects of a single session of exercise on insulin resistance that is caused by high fat availability is important, as it will provide valuable information regarding the mechanisms whereby exercise improves insulin sensitivity in obesity. Ultimately this could lead to improvements in the therapeutic and/or pharmacological treatment of obesity-related diseases such as diabetes.
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