ADIPOSE TISSUE, ADIPOKINES & APPETITE REGULATORY HORMONES IN CUSHING'S DISEASE

脂肪组织，脂肪因子

• 批准号: 7718149
• 负责人: ELIZA Brevoort GEER
• 金额: $ 0.57万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718149
• 关键词: Abdomen; Adipose tissue; Body Composition; Body fat; Computer Retrieval of Information on Scientific Projects Database; Deposition; Desire for food; Dose; Fasting; Fatty acid glycerol esters; Funding; Glucose; Grant; Hormones; Hunger; Hydrocortisone; Institution; Insulin; Leptin; Magnetic Resonance Imaging; Measures; Obesity; Operative Surgical Procedures; Patients; Pattern; Peripheral; Pituitary-dependent Cushing' s disease; Play; Postoperative Period; Questionnaires; Recruitment Activity; Research; Research Personnel; Resources; Role; Satiation; Score; Source; Steroids; Testing; Time; Tissues; United States National Institutes of Health; Visceral; Visit; adipokines; adiponectin; ghrelin

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. Cushing's disease is associated with profound body composition changes. These changes include an increase in central versus peripheral fat deposition. After surgical treatment of Cushing's, over time the body composition changes normalize. These changes in body composition are felt to be due to direct actions of cortisol on fat tissue, but new research has shown that other hormones may be involved as well. Adipokines (leptin and adiponectin) as well as appetite hormones (ghrelin and PYY) seem to play a role in appetite and obesity. This study proposes to investigate the role of these hormones in the body composition changes seen in Cushing's. We plan to follow 20 Cushing's patients over time before and after surgical treatment. There will be one pre-operative and two post-operative visits, the first post-operative visit while the patient has been on a stable dose of steroids for at least 6 months and the second while the patient has been off steroids for at least 6 months. We will measure fasting leptin and adiponectin as well as glucose, insulin, PYY, and ghrelin before and at 30, 60, 90, 120, and 180 minutes after a test meal. Subjects will complete a questionnaire before and after the test meal to measure levels of hunger and satiety. We will also recruit 10 control patients to undergo these hormone tests during one study visit. In the Cushing's patients, we will investigate adipose distribution by whole-body MRI, to correlate the changes in hormone levels with body composition changes that occur with treatment of Cushing's disease. Hypothesis 1: Compared to BMI-matched controls, patients with active Cushing's disease will have low fasting ghrelin levels that fail to display normal suppression after a meal, which will resolve after surgical cure. Hypothesis 2: Compared to BMI-matched controls, patients with active Cushing's disease will have low fasting PYY levels with a blunted meal-induced rise, which will resolve after surgical cure. Hypothesis 3: Abnormal patterns in ghrelin and PYY will correlate to higher hunger scores and lower satiety scores in untreated Cushing's compared to controls; this will normalize after surgery. Hypothesis 4: Adiponectin will be relatively more suppressed and leptin will be relatively higher in Cushing's disease compared to BMI-matched controls. Hypothesis 5: Abdominal and visceral fat will be increased in Cushing's disease compared to matched controls. Normalization of body fat distribution post-surgery will correspond to changes in adipokine levels.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 库欣病与身体成分的深刻变化有关。 这些变化包括中央与外周脂肪沉积的增加。 经过手术治疗的库欣，随着时间的推移，身体组成的变化正常化。 身体成分的这些变化被认为是由于皮质醇对脂肪组织的直接作用，但新的研究表明，其他激素也可能参与其中。 脂肪因子（瘦素和脂联素）以及食欲激素（生长激素释放肽和PYY）似乎在食欲和肥胖中起作用。 本研究旨在探讨这些激素在库欣氏症患者体内成分变化中的作用。 我们计划随访20例库欣病患者手术前后的情况。 将进行一次术前访视和两次术后访视，第一次术后访视时患者已接受稳定剂量的类固醇至少6个月，第二次术后访视时患者已停用类固醇至少6个月。 我们将测量空腹瘦素和脂联素以及葡萄糖，胰岛素，PYY和ghrelin在测试餐前和测试餐后30，60，90，120和180分钟。 受试者将在试验餐前后完成问卷调查，以测量饥饿和饱腹感水平。 我们还将招募10名对照患者，在一次研究访视期间接受这些激素检测。 在库欣病患者中，我们将通过全身MRI研究脂肪分布，以将激素水平的变化与库欣病治疗中发生的身体成分变化相关联。 假设1： 与BMI匹配的对照组相比，活动性库欣病患者的空腹胃饥饿素水平较低，餐后不能显示正常的抑制，手术治愈后将消退。 假设二： 与BMI匹配的对照组相比，活动性库欣病患者的空腹PYY水平较低，餐后升高不明显，手术治愈后将消退。 假设三： 与对照组相比，未治疗的库欣氏病患者中生长激素释放肽和PYY的异常模式将与更高的饥饿评分和更低的饱腹评分相关;这将在手术后恢复正常。 假设4： 与BMI匹配的对照组相比，库欣病患者的脂联素将受到相对更多的抑制，瘦素将相对较高。 假设五： 与匹配的对照组相比，库欣病患者的腹部和内脏脂肪会增加。术后体脂分布的正常化将对应于脂肪因子水平的变化。