Childhood overweight is a strong predictor of adult obesity. Abnormalities in glucose and lipid homeostasis are associated with body weight gain and many o f the alterations found in the Metabolic Syndrome. Obese sedentary adults, in particular obese African Americans, are more prone to hyperglycemia, hyperinsulinemia, lower rates of post- absorptive adipose tissue lipolysis per unit fat mass, poor post- prandial suppression of lipolysis and reduced blood flow. We propose to implement the novel use of microdialysis to assess interstitial glucose and glycerol concentrations as indices of blood glucose and adipose tissue lipolysis, respectively, and adipose tissue blood flow in lean and obese prepubescent children continuously over 24 hours. The hypothesis is that overweight children exhibit higher interstitial glucose concentrations throughout the day, reduced rates of basal lipolysis and poor postprandial suppression of lipolysis compared to lean children, and that these abnormalities will be associated with a higher prevalence of cardiovascular disease risk factors. Furthermore, 16- weeks of physical activity will normalize, or bring closer to lean, the glucose and lipolytic profiles of overweight children and will result in an improved cardiovascular disease risk profile. We will investigate lean and overweight African American and Caucasian children (8- 10 yr; n=80) before and after 16 weeks of increased physical activity. Subcutaneous abdominal adipose tissue lipolysis and glucose profiles will by monitored using microdialysis under resting fasting and fed conditions as well as in response to exercise. Microdialysis probes will be perfused with either a control solution, an inhibitor of nitric oxide synthase (L- NMMA), or an activator of nitric oxide synthase (acetylcholine) to investigate the mechanism of the proposed reduction of basal lipolysis in obese and African American children. These investigations will determine if acute and chronic aerobic physical activity improves the lipolytic and glucose profiles in lean and overweight children, and whether these beneficial changes will be accompanied by improvements in cardiovascular disease risk factors. The long- term objectives are: 1) to identify the relevant in- vivo metabolic and circulatory parameters that are deficient in overweight children and adults that place them at risk for metabolic and cardiovascular disease; and 2) to find practical means of reversing metabolic and circulatory insufficiencies in obese individuals, thereby reducing the incidence of metabolic and cardiovascular diseases. ? ?
