FAT DISTRIBUTION AND INSULIN RESISTANCE IN HIV

肌肉抑制素、解偶联蛋白和血管紧张素转换酶基因的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体最大的肌间隔区，日益成为分子遗传学和临床研究的热点。尽管有这种强烈的研究兴趣，但非侵入性地表征局部和全身骨骼肌的分布、质量和组成的方法仍然非常有限。这项研究的第一阶段在项目II中开发和改进了骨骼肌评估方法和模型，对正常和超重的混血成年人进行了横断面队列研究。在成人实现这一目标的过程中，我们使用参考体成分方法观察和报告了以下情况：老年人的相对骨骼肌量低于年轻受试者；骨骼肌量低于年轻受试者；骨骼肌量和分布是性别、年龄和身体质量的函数；在所有成年年龄，非裔美国人的骨骼肌和相关骨骼间隔比高加索人大，即使在控制了其他已知的骨骼肌决定因素后也是如此。以这些生物学观察为基础，我们验证、改进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的方法、双能X射线吸收法、40K计数、生物阻抗分析、人体测量和尿代谢物标志物。这些努力促成了与其他项目成员的重要合作，在核心单位开发了新的实验室资源，并与在新的哥伦比亚生物医学工程系具有建模经验的工程师进行了接触。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的成年人中开发的，而不是在身体质量极端时；我们的方法仅在横断面样本中得到验证，而不是在纵向队列中得到验证，这些纵向队列中的骨骼肌变化继发于儿童的生长或干预。所有这三个领域的临床和研究重要性导致我们提出了6个新的假设和相关的目标，分为3个独立的人类和动物研究。：研究1建议在Tanner阶段1-5的240名非裔美国人和高加索男性和女性中推进方法开发；48人将在2-3年随访增长；研究2建议在项目2和3中交叉验证体重不足(神经性厌食症)和肥胖的成年患者的模型，在旨在产生体重变化的治疗之前和期间；研究3旨在非侵入性地评估所有四个项目的受试者整个生命周期中肌肉组成的各个方面；并首次建立特定的基于假设的干预措施之前和之后的啮齿动物骨骼肌的相关电特性。此外，为了与项目互动，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。复合开发的方法和它们涉及的生物学问题将为预期在不久的将来进行的人类骨骼肌研究，特别是在儿童中的研究提供基础。

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.