LIPID ACCUMULATION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在过去的一代人中，肥胖症的患病率一直在上升，是一个严重的公共卫生问题。肥胖是心血管疾病、中风、某些类型的癌症和2型糖尿病的重要危险因素。肥胖通过胰岛素抵抗导致2型糖尿病。虽然有强有力的证据表明胰岛素敏感度的下降和身体脂肪组织的增加之间存在相关性，但体脂和胰岛素受体敏感度之间的总体机制联系仍然难以捉摸。在体脂和外周胰岛素作用之间的关系中，区域性脂肪分布也被认为是一个调节因素。最近的一个考虑是在脂肪组织隔间之外的器官特异性脂肪积累。特别是，骨骼肌中的脂肪酸积累可能会对以葡萄糖摄取衡量的全身胰岛素作用产生深远影响，因为该组织在体内对胰岛素反应的葡萄糖利用中所占比例最大。这项拟议的研究将提供有关心肌细胞内脂质(IMCL)在与肥胖相关的胰岛素抵抗中的作用的定量信息。首先，它将评估减肥对一组健康肥胖成年人的IMCL和胰岛素抵抗的影响。其次，它将探索肥胖组和其他相似的瘦人组的胰岛素抵抗与IMCL、BMI、全身脂肪(TBF)和血清甘油三酯(TG)水平的相关性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity has been increasing in prevalence the past generation and is a serious public health problem. Obesity is an important risk factor for cardiovascular disease, stroke, some types of cancer, and type 2 diabetes. Obesity leads to type 2 diabetes through insulin resistance. While there is strong evidence of a correlation between the decline in insulin sensitivity and the increase in body adipose tissue, the overall mechanistic association between body fat and insulin receptor sensitivity remains elusive. Regional fat distribution has been also considered as a modulating factor in the relationship between body fat and peripheral insulin action. A more recent consideration has been organ-specific fat accumulation, outside of the adipose tissue compartment. In particular, fatty acid accumulation in skeletal muscle may have a profound influence in whole-body insulin action measured by glucose uptake, since that tissue accounts for the largest proportion of insulin-responsive glucose utilization in the body. The proposed study will provide quantitative information on the contribution of intramyocellular lipid (IMCL) to insulin resistance associated with obesity. First, it will assess the effects of weight loss on the IMCL and insulin resistance of a group of healthy obese adults. Second, it will explore the correlation between insulin resistance and IMCL, BMI, total body fat (TBF), and serum triglyceride (TG) levels of the obese group with an otherwise similar group of lean individuals.