Regulation of lipolysis by nitric oxide and adenosine

一氧化氮和腺苷调节脂肪分解

• 批准号: 7072473
• 负责人: ROBERT C HICKNER
• 金额: $ 21.38万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072473
• 关键词: African American; abdomen; adenosine; adipose tissue; biological signal transduction; caucasian American; clinical research; disease /disorder etiology; enzyme inhibitors; exercise; female; human subject; isoproterenol; lipolysis; microdialysis; neurotransmitter receptor; nitric oxide; nitric oxide synthase; obesity; patient oriented research; racial /ethnic difference; women' s health; young adult human (21-34)

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.

描述（由申请人提供）：非裔美国妇女的肥胖率高于经济和教育状况相似的高加索妇女。在相同的减肥方案下，非洲裔美国妇女减肥较少，减肥速度比白人妇女慢。有体内证据表明，这些差异的原因之一是非洲裔美国妇女的脂肪库动员减少。然而，来自体外研究的证据表明，脂肪细胞的脂解作用在非洲裔美国人和高加索妇女中是相似的。这些不同的体内和体外反应表明，存在体内脂解抑制剂，这可能是非裔美国妇女体内脂解率较低的原因。可解释这些差异的人体内脂解的潜在体内调节剂是一氧化氮（NO）和腺苷，其已显示在体内抑制脂肪组织中的脂解。我们的假设是，一氧化氮依赖性和/或腺苷依赖性抑制脂肪组织中的脂解是更大的非裔美国人比白人妇女在休息和急性应激的运动。本申请的目的是确定：1）一氧化氮是否通过抑制脂解信号级联中的特定单个步骤而在非裔美国人中比在高加索人女性中更大程度地降低脂解活性;和2）腺苷是否在非裔美国人女性中比在高加索人女性中更大程度地抑制脂解。为了解决这些问题，12名肥胖的非洲裔美国人和12名肥胖的白人妇女将进行研究，使用微透析监测脂肪组织脂解在皮下腹部脂肪组织中的存在和不存在的脂解级联的激活剂和存在和不存在的一氧化氮合酶或腺苷受体的抑制剂。在不存在和存在脂解级联激活剂的情况下，在存在和不存在一氧化氮合酶刺激或腺苷受体刺激的情况下，还将对腹部手术期间获得的腹部皮下和网膜脂肪组织进行体外脂解，以解决脂解反应中的贮库特异性差异。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高加索妇女肥胖的策略。