FAT DISTRIBUTION AND INSULIN RESISTANCE IN HIV

HIV 中的脂肪分布和胰岛素抵抗

• 批准号: 6651313
• 负责人: DONALD P KOTLER
• 金额: $ 14.86万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651313
• 关键词: AIDS; AIDS therapy; HIV infections; adipose tissue; age difference; antiAIDS agent; bioenergetics; body composition; cachexia; clinical research; combination chemotherapy; drug adverse effect; exercise; gender difference; glucose clamp technique; human subject; human therapy evaluation; insulin sensitivity /resistance; magnetic resonance imaging; medical complication; morphometry; phenotype; somatotropin; troglitazone

Myostatin, uncoupling proteins, and ACE polymorphisms are recently discovered regulators of skeletal muscle growth, metabolism, and function. Skeletal muscle, the largest body compartment in normal weight humans, is increasingly a research focus of molecular genetic, and clinical investigations. Despite this intense research interest, methods of non-invasively characterizing regional and total body skeletal muscle distribution, mass, and composition remain remarkably limited. The first phase of this study in Program Project II developed and refined skeletal muscle evaluation methods and models in a cross-sectional cohort of normal and overweight ethnically-mixed adults. In progressing towards this aim in adults we observed and reported, using reference body composition methods, that; older adults have less relative skeletal muscle mass than young subjects; that skeletal muscle mass than young subjects; that skeletal muscle mass and distribution are functions of gender, age, and body mass; and that at all adult ages, African Americans have a larger skeletal muscle and related bone compartment than Caucasians, even after controlling for other known skeletal muscle determinants. With these biological observations as a basis, we validated, improved older, or developed new skeletal muscle mass measurement methods including those based on magnetic resonance imaging, or developed new skeletal muscle mass measurement methods including those based on magnetic resonance imaging, dual-energy x-ray absorptiometry, 40K counting, bioimpedance analysis, anthropometry, and urinary metabolite markers. These efforts led to important collaborations with members of the other projects, development of new laboratory resources in the core units, and outreach to engineers with modeling experience in the new Columbia Department of Biomedical Engineering. Important gaps, however, remain: our method and models are applicable only in adults; models were developed in normal and overweight adults and not at body mass extremes; and our methods were validated only in cross-sectional samples and not in longitudinal cohorts with skeletal muscle changes secondary to growth in children or interventions. The clinical and research importance of all 3 of these areas led us to advance 6 new hypotheses and related aims divided into 3 separate human and animal studies.: Study 1 proposes to advance method development in 240 African American and Caucasian males & females in Tanner Stages 1-5; 48 will be followed up at 2-3 years with growth; Study 2 proposes to cross-validate models in adult patients with underweight (anorexia nervosa) and obesity, in Projects 2 and 3, before and during treatments designed to produce weight change; Study 3 is designed to non-invasively evaluate aspects of muscle composition across the human lifespan in subjects from all four projects; and to establish, for the first time, relevant electrical properties of isolated rodent skeletal muscle before and following specific hypothesis-based interventions. In addition, to interact projects, this study will also provide important new information on adiposity and energy expenditure-related issues in children. The composite developed methods and the biological issues that they touch upon would provide a foundation for human skeletal muscle studies anticipated in the near future, particularly in children.

肌肉生长抑制素、解偶联蛋白和 ACE 多态性是最近发现的骨骼肌生长、代谢和功能的调节因子。骨骼肌是正常体重人类最大的身体部位，越来越成为分子遗传学和临床研究的研究重点。尽管研究兴趣浓厚，但非侵入性表征局部和全身骨骼肌分布、质量和成分的方法仍然非常有限。计划项目 II 中这项研究的第一阶段在正常和超重的种族混合成年人的横断面队列中开发和完善了骨骼肌评估方法和模型。在成人实现这一目标的过程中，我们使用参考身体成分方法观察并报告：老年人的相对骨骼肌质量比年轻受试者少；骨骼肌质量高于年轻受试者；骨骼肌质量和分布是性别、年龄和体重的函数；在所有成年年龄段，即使在控制了其他已知的骨骼肌决定因素之后，非裔美国人也比白人拥有更大的骨骼肌和相关骨室。以这些生物学观察为基础，我们验证、改进了旧的或开发了新的骨骼肌质量测量方法，包括基于磁共振成像的方法，或开发了新的骨骼肌质量测量方法，包括基于磁共振成像、双能x射线吸收测定法、40K 计数、生物阻抗分析、人体测量学和尿液代谢物标记物。这些努力促成了与其他项目成员的重要合作、核心单位新实验室资源的开发，以及在新的哥伦比亚生物医学工程系与具有建模经验的工程师的接触。然而，重要的差距仍然存在：我们的方法和模型仅适用于成年人；模型是在正常和超重成年人中开发的，而不是在体重极端情况下开发的；我们的方法仅在横截面样本中得到验证，而不是在因儿童生长或干预措施而导致骨骼肌变化的纵向队列中得到验证。所有这 3 个领域的临床和研究重要性使我们提出了 6 个新假设和相关目标，分为 3 个单独的人类和动物研究。：研究 1 提议在 Tanner 阶段的 240 名非裔美国人和白人男性和女性中推进方法开发1-5； 48将随访2-3年有生长；研究 2 提议在项目 2 和 3 中，在旨在产生体重变化的治疗之前和治疗期间，对体重不足（神经性厌食症）和肥胖的成年患者进行模型交叉验证；研究 3 旨在以非侵入性方式评估所有四个项目的受试者在整个人类生命周期中的肌肉成分； 并首次确定离体啮齿动物骨骼肌在基于特定假设的干预之前和之后的相关电特性。此外，为了互动项目，这项研究还将提供有关儿童肥胖和能量消耗相关问题的重要新信息。该复合材料开发的方法及其涉及的生物学问题将为预计在不久的将来进行的人类骨骼肌研究（特别是儿童骨骼肌研究）奠定基础。