Regulation of lipolysis by nitric oxide and adenosine

East Carolina University, Greenville NC

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): Obesity rates are higher in African American women than Caucasian women of similar economic and educational status. African American women lose less weight and lose weight at a slower rate than Caucasian women under the same weight-loss regimen. There is in-vivo evidence to suggest that one of the causes of these differences is a decreased mobilization of fat depots in African American women. However, evidence from in-vitro studies shows that lipolysis by adipocytes is similar in African American and Caucasian women. These differential in-vivo and in-vitro responses suggest that there are in-vivo inhibitors of lipolysis that may account for the lower in-vivo rates of lipolysis in African American women. Potential in- vivo regulators of lipolysis in humans that may account for these differences are nitric oxide (NO) and adenosine, which have been shown to suppress lipolysis in-vivo in adipose tissue. Our hypothesis is that nitric oxide-dependent and/or adenosine-dependent suppression of lipolysis in adipose tissue are greater in African American than Caucasian women at rest and in response to acute stress of exercise. The purpose of this application is to determine: 1) if nitric oxide reduces lipolytic activity by inhibiting specific individual steps in the lipolytic signaling cascade to a greater extent in African American than Caucasian women; and 2) if adenosine suppresses lipolysis in African American women to a greater extent than in Caucasian women. To address these issues, 12 obese African American and 12 obese Caucasian women will be studied using microdialysis to monitor adipose tissue lipolysis in subcutaneous abdominal adipose tissue in the absence and presence of activators of the lipolytic cascade and in the absence and presence of an inhibitor of nitric oxide synthase or the adenosine receptors. In-vitro lipolysis, in the absence and presence of activators of the lipolytic cascade, with and without nitric oxide synthase stimulation or adenosine receptor stimulation, will also be conducted on abdominal subcutaneous and omental adipose tissue obtained during abdominal surgery to address depot-specific differences in lipolytic response. Understanding the differences in fat utilization will provide insight into the potential causes of obesity and help in designing strategies for the control and prevention of obesity in African American and Caucasian women. [unreadable] [unreadable] [unreadable]