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体最大的隔室，已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，非侵入性表征区域和全身骨骼肌分布、质量和组成的方法仍然非常有限。本研究项目II的第一阶段在正常和超重混血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。在向这一目标迈进的成年人中，我们观察和报告，使用参考身体成分方法，；老年人的相对骨骼肌量比年轻人少；即骨骼肌量大于年轻受试者；骨骼肌的数量和分布是性别、年龄和体重的函数；在所有成年阶段，非裔美国人的骨骼肌和相关骨间隔都比白种人大，即使在控制了其他已知的骨骼肌决定因素之后也是如此。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骨骼肌质量测量方法，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线吸收仪、40K计数、生物阻抗分析、人体测量和尿代谢标志物的骨骼肌质量测量方法。这些努力促成了与其他项目成员的重要合作，在核心单元开发了新的实验室资源，并在新成立的哥伦比亚生物医学工程系向具有建模经验的工程师伸出了援手。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得到验证，而没有在骨骼肌变化继发于儿童生长或干预的纵向队列中得到验证。这三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个单独的人类和动物研究。研究1建议在240名非洲裔美国人和白人男性和女性的Tanner阶段1-5中推进方法开发；48个将在2-3年后进行后续发展；研究2建议交叉验证项目2和项目3中体重过轻（神经性厌食症）和肥胖的成年患者在治疗前和治疗期间的模型，以改变体重；研究3旨在非侵入性地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组成方面；并首次建立了在特定假设干预之前和之后分离的啮齿动物骨骼肌的相关电特性。此外，本研究还将为儿童肥胖和能量消耗相关问题提供重要的新信息。复合开发的方法和他们所涉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.