FAT DISTRIBUTION AND INSULIN RESISTANCE IN HIV

肌生长抑制素、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群中最大的身体部位，越来越成为分子遗传学和临床研究的焦点。尽管有这种强烈的研究兴趣，非侵入性表征局部和全身骨骼肌分布，质量和组成的方法仍然非常有限。本研究的第一阶段在项目II中开发和完善了正常和超重种族混合成年人的横截面队列中的骨骼肌评估方法和模型。在成人中朝着这一目标前进的过程中，我们使用参考身体组成方法观察并报告了：老年人的相对骨骼肌质量低于年轻受试者;骨骼肌质量低于年轻受试者;骨骼肌质量和分布是性别、年龄和体重的函数;在所有的成年年龄段，非洲裔美国人的骨骼肌和相关的骨室都比白人大，即使在控制了其他已知的骨骼肌决定因素之后。以这些生物学观察结果为基础，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射线吸收法、40 K计数、生物阻抗分析、人体测量和尿代谢物标记物的方法。这些努力导致了与其他项目成员的重要合作，在核心单位开发新的实验室资源，并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进行外联。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的成年人中开发的，而不是在体重极端的情况下;我们的方法仅在横断面样本中进行了验证，而不是在儿童生长或干预措施继发骨骼肌变化的纵向队列中。所有这3个领域的临床和研究重要性使我们提出了6个新的假设和相关目标，分为3个独立的人类和动物研究。研究1建议在坦纳1-5期的240名非洲裔美国人和高加索男性和女性中推进方法开发; 48名将在2-3年随生长进行随访;研究2建议在体重不足的成年患者中交叉验证模型（神经性厌食症）和肥胖，在项目2和3中，在旨在产生体重变化的治疗之前和期间;研究3的目的是非侵入性地评估所有四个项目的受试者在整个人类寿命期间的肌肉组成方面;并首次在特定的基于假设的干预之前和之后建立分离的啮齿动物骨骼肌的相关电特性。此外，互动项目，这项研究还将提供重要的新信息，肥胖和能源消耗相关的问题，在儿童。复合开发的方法和他们触及的生物学问题将为不久的将来预期的人类骨骼肌研究提供基础，特别是在儿童中。

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.