LIPID METABOLISM IN OBESITY, WEIGHT LOSS AND EXERCISE

描述：（改编自申请人摘要）：长期目标 这项研究是为了更好地了解人类骨骼肌的缺陷， 导致肥胖症的发病率和死亡率。有 有证据表明，肥胖个体骨骼肌中的脂质代谢 以有利于脂质储存的方式改变。例如，一些数据显示， 肥胖的骨骼肌氧化脂质的能力降低。有 也有证据表明，肌肉相关的甘油三酯浓度增加， 肥胖这些都是重要的观察结果，因为脂质的积累， 骨骼肌与胰岛素抵抗有关。脂质在体内的储存 因此骨骼肌可能使肥胖个体易于发生胰岛素抵抗 以及与胰岛素抵抗相关的许多疾病（高血压、冠状动脉粥样硬化）， 动脉疾病、糖尿病）。尽管有这些重要的影响， 促进肥胖骨骼肌中脂质积聚的细胞机制是 不明显。在当前的应用实验中，提出将 确定促进骨骼中脂质储存的机制 肌肉与肥胖，如果干预补偿或纠正最初的 缺陷。主要假设是吸收后（空腹）脂质 骨骼肌中的代谢随着肥胖而改变， 脂肪堆积在这个组织里。这一假设是基于初步的 工作，其中观察到脂质氧化在肌肉中被抑制， 肥胖个体与氧化酶减少 活动这些初步数据构成了工作假设的基础 脂肪氧化在肥胖的骨骼肌中被抑制， 促进脂质储存。第二个假设是，减肥并不 增强脂质氧化，但减少肌肉甘油三酯储存， 替代机制。第三个假设是运动训练 逆转肥胖症明显的脂质氧化的初始减少， 促进脂质利用。为了检验这些假设，将确定： 特定目的I -如果骨骼肌吸收后脂质代谢受损 肌肉从肥胖的个人在一种方式，促进积累的 脂质;特定目的II -如果吸收后脂质代谢受损 在肥胖个体的骨骼肌中， 具体目标III -如果运动训练增强 肥胖者吸收后脂质代谢和细胞内脂质代谢 机制负责。调查结果将是重要的，因为很少有人知道 关于负责脂质代谢缺陷的机制， 肥胖和干预的影响。

DESCRIPTION: (Adapted from the applicant's abstract):The long-term objective of this research is to better understand defects in human skeletal muscle that contribute to the morbidity and mortality evident with obesity. There is evidence that lipid metabolism in the skeletal muscle of obese individuals is altered in a manner favoring lipid storage. For example, some data indicate that obese skeletal muscle has a reduced capacity to oxidize lipid. There is also evidence that muscle-associated triglyceride concentration increases with obesity. These are important observations as the accumulation of lipid in skeletal muscle is associated with insulin resistance. The storage of lipid in skeletal muscle may thus predispose obese individuals toward insulin resistance and the many conditions linked with insulin resistance (hypertension, coronary artery disease, diabetes mellitus). Despite these important implications, the cellular mechanism that promotes lipid accretion in obese skeletal muscle is not evident. In the current application experiments are proposed that will determine the mechanism(s) responsible for promoting lipid storage in skeletal muscle with obesity and if intervention compensates or corrects the initial defect(s). The primary hypothesis is that postabsorptive (fasting) lipid metabolism in skeletal muscle is altered with obesity in a manner that promotes lipid accumulation in this tissue. This hypothesis is based upon preliminary work, where it was observed that lipid oxidation is depressed in the muscle of obese individuals in conjunction with reductions in oxidative enzyme activities. These preliminary data form the basis for the working hypothesis that lipid oxidation is depressed in skeletal muscle with obesity which promotes lipid storage. The secondary hypothesis is that weight loss does not enhance lipid oxidation, but reduces muscle triglyceride stores by an alternative mechanism. The tertiary hypothesis is that exercise training reverses the initial decrement in lipid oxidation evident with obesity, promoting lipid utilization. To test these hypotheses it will be determined: Specific Aim I - if postabsorptive lipid metabolism is impaired in skeletal muscle from obese individuals in a manner that promotes the accumulation of lipid; Specific Aim II - if the impairment in postabsorptive lipid metabolism in the skeletal muscle of obese individuals is corrected or compensated for with weight loss and; Specific Aim III - if exercise training enhances postabsorptive lipid metabolism in obese individuals and the cellular mechanisms responsible. Findings will be important as little is known concerning the mechanisms responsible for the defects in lipid metabolism with obesity and the impact of intervention.