Obesity, sedentariness and aging are associated with declines in lipid, glucose and adipose tissue metabolism, and altered sympathoadrenal responsiveness. To determine the interrelationships among these variables, this study examines metabolic and sympathoadrenal functions in healthy, obese, sedentary men aged 45-75 years at entry into the study and after weight reduction or aerobic exercise training. The metabolic function evaluated are: 1) glucose tolerance; 2) insulin secretion and sensitivity assessed by euglycemic and hyperglycemic clamps; 3) lipoprotein lipid profiles, high density lipoprotein (HDL) subspecies levels, and postheparin plasma lipoprotein lipase and hepatic lipase activity; 4) the regulation of adipose tissue lipolysis and fat cell size by physical fitness (V02max), fatness (% body fat), and the regional distribution of body fat (waist:hip circumferential ratio) by measuring the responsiveness of biopsied adipose tissue from upper and lower body sites to beta- and alpha2-adrenergic stimuli and by the activity of lipoprotein lipase; and 5) sympathoadrenal responses to upright posture. A total of 152 subjects have completed baseline metabolic studies and have been randomized to either the weight reduction or aerobic exercise training interventions. Thirty-eight subjects have completed the weight loss program and 27 the exercise program. With weight loss of >5% body weight with no change in V02max, there was a significant improvement in most of the metabolic variables. In 27 subjects whose V02max increased >10%, triglyceride decreased but other metabolic variables did not change. Subjects completing both interventions demonstrated complementary effects on metabolic function. In addition to the subjects who have completed their interventions, there are currently 31 subjects in progress in the weight loss group and 33 in the exercise group. These metabolic studies are a collaborative effort of scientists in the Metabolism Section, LCP, NIA and in the Division of Geriatric Medicine and Gerontology, Department of Medicine, the Johns Hopkins University.