INHIBITION OF CORTISONE FORMATION IN CENTRAL OBESITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。可的松的活性形式是皮质醇，一种在肾上腺中产生的物质。皮质醇被肾脏灭活，形成非活性可的松，可的松在肝脏和脂肪组织中被重新激活，以改造活性皮质醇。最近的证据表明，肥胖个体的脂肪细胞增加了可重新激活可的松的酶的活性。由于皮质醇的过量产生会导致腹部肥胖，因此这种再激活过程的过度活跃可能是导致某些人肥胖恶化的原因。为了确定这一途径的重要性，我们计划使用甘草提取物阻断可的松在肾脏中的形成。如果可的松在脂肪细胞中的再激活是引起腹部肥胖的重要因素，那么抑制可的松的形成应该会导致腹部脂肪的减少。我们将研究六名腹部肥胖的女性。每位受试者将接受为期六个月的甘草提取物治疗。我们将在治疗前和治疗期间测量体重、腹部脂肪和全身脂肪含量、糖、胰岛素、胆固醇和血压。已知的甘草副作用包括盐潴留、血压升高和钾流失。为了防止这些副作用，我们将使用螺内酯和甘草提取物。螺内酯能有效抑制甘草的高血压、盐潴留和耗钾作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The active form of cortisone is cortisol, a substance made in the adrenal glands. Cortisol is inactivated by the kidney to form inactive cortisone, and cortisone is reactivated in liver and fat tissue to reform active cortisol. Recent evidence suggests that fat cells in obese individuals have increased activity of the enzyme that reactivates cortisone. Since overproduction of cortisol causes abdominal obesity, it is possible that the overactivity of this reactivation process is responsible for worsening obesity in some individuals. In order to determine the importance of this pathway, we plan to block the formation of cortisone in the kidney using a licorice extract. If reactivation of cortisone in fat cells is important in causing abdominal obesity, inhibition of cortisone formation should cause a decrease in abdominal fat. We will study six women with abdominal obesity. Each subject will be treated with licorice extract for six months. We will measure weight, abdominal and total body fat content, sugar, insulin, cholesterol and blood pressure before treatment and during treatment. Known side effects of licorice include salt retention, increased blood pressure and potassium loss. In order to prevent these side effects, we will administer spironolactone along with the licorice extract. Spironolactone is an effective inhibitor of the hypertensive, salt retaining effects and potassium wasting effects of licorice.