Although much has been learned about the hormonal and substrate factors controlling adipose tissue lipolysis, as measured by plasma FFA flux, our understanding of what regulates FFA release individuals remains imperfect. Although FFA are known to be an energy source, presumably regulated to meet energy demands, FFA flux values are instead normalized to body weight, lean body mass, body fat mass, or body cell mass. These different choices of data presentation exert a major influence on the interpretation of results and have resulted in serious disagreements as to what constitutes """"""""normal"""""""" FFA availability. We propose that the best physiologic predictor of FFA flux in lean, healthy adults will be resting energy expenditure, as assessed by basal VO2. If this is true, an improved understanding of what constitutes excess FFA release will be possible. This distinction is important because when excess lipolysis occurs, liver and muscle are over exposed to FFA. This may result in reduced hepatic insulin clearance, hyperlipidemia, and insulin resistance, all metabolic complications of obesity. Thus, it is possible that excess plasma FFA availability mediate many of the adverse consequences of obesity and diabetes, either directly or through the overfilling of intramuscular triglyceride pools. The objectives of this proposal are to define the major determinants of FFA flux and examine liver and muscle FFA metabolism. Specifically, these studies will determine whether: 1) differences in resting energy expenditure, as reflected by differences in basal VO2, predict inter-individual differences in average basal FFA flux in lean, healthy adults; 2) gender and race (Caucasian vs African-American) influence the relationship between average VO2 and average basal FFA flux; 3) obesity, upper body fat distribution and increased fat cell size increase average basal FFA flux relative to VO2 in Caucasian and African-American adults; 4) hepatic FFA delivery is increased in NIDDM/hypertriglyceridemic individuals (obese and non-obese) compared with glucose tolerant, normolipidemic individuals (obese and non-obese); 5) intracellular muscle fatty acid specific activity and fractional turnover rates predicted from leg arterio-venous difference techniques correlate with values obtained from muscle biopsy of the same leg; and 6) intracellular fatty acid fractional turnover rates and pools sizes in muscle are greater in obese, glucose intolerant and lean, glucose tolerant individuals.
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