Regulation of lipolysis by nitric oxide and adenosine

描述（由申请人提供）：非洲裔美国女性的肥胖率高于同等经济和教育水平的白人女性。在同样的减肥方案下，非裔美国女性比白人女性减重更少，减重速度也更慢。有活体证据表明，这些差异的原因之一是非洲裔美国妇女脂肪库的动员减少。然而，来自体外研究的证据表明，脂肪细胞的脂肪分解在非裔美国人和白种人妇女中是相似的。这些体内和体外反应的差异表明，体内存在脂肪分解抑制剂，这可能是非洲裔美国妇女体内脂肪分解率较低的原因。一氧化氮（NO）和腺苷可能是人体体内脂肪分解的潜在调节因子，可以解释这些差异，它们已被证明可以抑制体内脂肪组织中的脂肪分解。我们的假设是，非裔美国女性在休息时和对急性运动压力的反应中，脂肪组织中一氧化氮依赖和/或腺苷依赖的脂肪分解抑制比白人女性更大。本应用的目的是确定：1)在非裔美国妇女中，一氧化氮是否通过更大程度地抑制脂溶信号级联中的特定个体步骤来降低脂溶活性；2)腺苷对非裔美国女性脂肪分解的抑制程度是否大于白人女性。为了解决这些问题，将对12名肥胖的非裔美国人和12名肥胖的高加索女性进行研究，在脂肪分解级联激活剂缺失和存在以及一氧化氮合酶抑制剂或腺苷受体缺失和存在的情况下，使用微透析监测皮下腹部脂肪组织的脂肪分解。体外脂解，在有无脂解级联激活剂的情况下，在有或没有一氧化氮合酶刺激或腺苷受体刺激的情况下，也将对腹部手术中获得的腹部皮下和网膜脂肪组织进行，以解决脂解反应的储存库特异性差异。了解脂肪利用的差异将有助于深入了解肥胖的潜在原因，并有助于设计控制和预防非裔美国人和白种人妇女肥胖的策略。

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.