STUDIES OF REGIONAL FAT DISTRIBUTION AND ENERGY BALANCE

本申请中的研究旨在更好地了解人体脂肪量的调节和决定人体脂肪分布的机制。提出了三个具体目标：1。以确定是否实验诱导或自发的血浆瘦素水平的变化预测随后的身体组成的变化。所采用的方案也将阐明高碳水化合物饮食诱导饱腹感和体重减轻的机制，以及老年人非自愿体重减轻的机制。2.研究中心体脂肪再分布、成脂基因表达变化与血脂和胰岛素敏感性致动脉粥样硬化变化之间的关系。这项工作的模型将是在接受积极的抗逆转录病毒治疗艾滋病毒感染的受试者中发生的体脂重新分布。3.确定解偶联蛋白（UCP）基因表达的变化是否能减弱饮食诱导的体脂量变化。本研究将使用为特定目标2开发的技术，以确定在人类受试者实验性体重增加和体重减轻后，肌肉和脂肪UCP表达是否与能量消耗平行变化。申请人已经成功地培训了几个年轻的医生研究人员以病人为导向的基础研究，并提出了一个计划，继续这样做。

The studies in this application are designed to better understand the regulation of body fat mass and the mechanisms determining body fat distribution in humans. Three Specific Aims are proposed: 1. To determine whether experimentally-induced or spontaneous variations in plasma leptin levels predict subsequent changes in body composition. The protocols employed will also elucidate the mechanism by which high carbohydrate diets induce satiety and weight loss, and the mechanism of involuntary weight loss in the elderly. 2. To examine the relationships among central body fat redistribution, changes in adipogenic gene expression, and atherogenic changes in plasma lipids and insulin sensitivity. The model for this work will be the body fat redistribution that occurs in subjects receiving aggressive antiretroviral therapy for HIV infection. 3. To determine whether changes in uncoupling protein (UCP) gene expression act to attenuate diet-induced changes in body fat mass. This study will use the technology developed for Specific Aim 2 to ascertain whether muscle and fat UCP expression change in parallel with energy expenditure following experimental weight gain and weight loss in human subjects. The applicant has successfully trained several young physician investigators in patient-oriented and basic research, and a plan to continue doing so is presented.