The proposed research will examine whether differences in regional adipose tissue fatty acid metabolism are present in humans. We have shown that upper body obesity in women is associated with increased FFA availability, and that the excess release can be localized to non-splanchnic, upper body adipose tissue. Excess FFA release is thought to result in some of the metabolic consequences of upper body obesity, especially if FFA are released directly into the portal circulation (i.e., from visceral adipose tissue) where they may have more exaggerated effects on hepatic glucose, insulin and lipid metabolism. Surprisingly, we were unable to document increased splanchnic FFA release in healthy upper body obese women. The proposed studies will determine whether increased hepatic FFA delivery is present in humans with noninsulin-dependent diabetes mellitus (NIDDM)/hypertriglyceridemia, whether gender specific differences are present in the regional regulation of adipose tissue FFA release, and whether there are regional differences in meal triglyceride fatty acid storage between men and women and between obese individuals with different body fat distributions. Specifically, these studies will 1) determine whether hepatic FFA delivery is increased in NIDDM/hypertriglyceridemic individuals (obese and non-obese) compared with glucose tolerant, normal lipidemic individuals (obese and non-obese); 2) net splanchnic FFA release in visceral upper body obesity is greater than that observed in subcutaneous upper body obesity; 3) regional differences in adipose tissue FFA release are present in non-obese men and women; 4) mixed beta-, alpha-adrenergic stimulation results in differential increases in regional adipose tissue FFA release compared with pure beta-adrenergic stimulation; 5) physiologic hyperinsulinemia results in equal suppression of regional adipose tissue FFA release in non-obese men and women; 6) regional storage of exogenous triglyceride fatty acids is similar following a """"""""bolus"""""""" meal and during a continuous enteral meal infusion in non-obese men and women; and 7) differences in regional triglyceride fatty acid storage from exogenous sources are associated with differences in body fat distribution in obese women before and after weight loss. These studies will provide new insights into the regulation of regional lipolysis in health and disease and will aid in the understanding of adipose tissue fatty acid storage and release in obese and non-obese men and women. It is hoped that this information will aid in the development of more disease specific therapy for obesity and related conditions.
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