The overall objective of this research proposal is to systemically evaluate the differences in free fatty acid (FFA) metabolism among obese persons with different body fat distributions, and non-obese persons. By using rigorous anthropomorphic criteria to characterize moderately overweight women as upper body or lower body obesity, I have been able to discern distinct differences in FFA metabolism between these two types of obesity and non-obese women. Specifically, I have found that a) FFA flux is normal in lower body obesity, but significantly increased in upper body obesity; b) resistance to the ability of insulin to suppress FFA flux and oxidation is present in both types of obese women; and c) epinephrine results in a subnormal lipolytic response in upper body obese women. These differences may be due to localized, as opposed to generalized, abnormalities in the regulation of adipose tissue depots. This proposal is designed to test the following two general, but related hypotheses: 1) regional differences in adipose tissue lipolysis are present in vivo which account for the variations in resting systemic FFA Flux observed among obese women with different body fat topography, and 2) these differences in regional fat accumulation are associated with different abnormalities of suppression and stimulation of lipolysis.
The specific aims of this proposal are: 1) To determine if contribution of peripheral adipose tissue to systemic lipolysis is less in upper body obese women than lower body obese and non-obese women; 2) To test whether regional variations in the ability of insulin to suppress lipolysis exist in obese and non obese women; 3) To learn if the increased FFA flux in upper body obesity is due to increased splanchnic release of FFA; 4) To determine whether the suppressibility of endogenous FFA and oxidation is impaired in upper body obese women during meal absorption; 5) To learn whether decreased sensitivity, decreased responsiveness, or both, is responsible for the insulin resistance with regards to suppression of FFA Flux and oxidation in upper body obese and lower body obese women: 6) To determine if the decreased lipolytic response to epinephrine seen in upper body obese women is due to decreased sensitivity or decreased responsiveness to epinephrine: 7) To examine whether the defect in the ability of upper body obese women to enhance lipolysis extends to exercise, a physiologic circumstance in which increased FFA availability is essential for optimal metabolic function.
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