EFFECT OF ANDROGEN REPLACEMENT ON FAT METABOLISM

Aging is associated with increased body fatness, particularly in the trunk. This change in body fat and body fat distribution correlates with insulin resistance, hypertension, dyslipidemia and diabetes mellitus. Reduced levels of circulating androgens in aging men are associated with insulin resistance and centralization of body fat, whereas reduced levels of DHEA are associated with an upper body fat distribution in both aging men and women. If physiologic replacement of reduced levels of testosterone (men) or DHEA (men and women) can reverse some of the aging related changes in body fat distribution and fatty acid metabolism, this could provide a means of improving health as the United States population continues to age. The present experiments will assess whether reversing the age-related decline in androgens and DHEA can have positive effects on body fat distribution and fatty acid metabolism in the elderly. To accomplish these goals, the proposed experiments will address the following specific aims: 1) to determine whether the changes in body fat experiments will address the following specific aims: 1) to determine whether the changes in body fat experiments will address the following specific aims: 1) to determine whether the changes in body fat distribution which occur with aging are associated with differences in systemic FFA availability, fatty acid oxidation, and regional adipose tissue meal fatty acid uptake; 2) to determine whether the change in fat distribution expected to occur with testosterone replacement therapy is associated with improvements in FFA metabolism, increased fatty acid oxidation, or changes in adipose tissue meal fatty acid uptake; 3) to determine whether DHEA replacement therapy in the elderly is associated with decreased body fat and upper-body fat and, if so, to assess DHEA's effects on FFA metabolism, fatty acid oxidation and regional adipose tissue meal fatty acid uptake. In order to address these specific aims we will use state-of-the-art body composition techniques, measures of adipose FFA release, assessments of fatty acid oxidation at rest, following meal consumption, and during exercise. In addition, we will apply a relatively new technique of determining regional adipose tissue meal fatty acid uptake to father information about potential mechanisms of fat redistribution.