LIPID METABOLISM IN OBESITY, WEIGHT LOSS AND EXERCISE

描述：(改编自申请人的摘要)： 这项研究是为了更好地了解人类骨骼肌中的缺陷 与肥胖明显相关的发病率和死亡率。的确有 肥胖个体骨骼肌脂代谢的证据是 以有利于储存脂肪的方式改变的。例如，一些数据表明 肥胖的骨骼肌氧化脂质的能力降低。的确有 也有证据表明，肌肉相关的甘油三酯浓度随着 肥胖。这些都是重要的观察结果，因为脂肪在体内的积累 骨骼肌与胰岛素抵抗有关。脂肪在人体内的储存 因此，骨骼肌可能使肥胖者更容易出现胰岛素抵抗。 以及与胰岛素抵抗有关的许多情况(高血压、冠心病 动脉疾病、糖尿病)。尽管有这些重要的影响，但 促进肥胖骨骼肌脂肪堆积的细胞机制是 不是很明显。在当前的应用中，提出的实验将 确定促进骨骼脂肪储存的机制(S) 肌肉肥胖，如果干预补偿或纠正了最初的 缺陷(S)。主要假设是吸收后(空腹)脂类 肥胖会改变骨骼肌的新陈代谢，从而促进 脂肪堆积在这个组织中。这一假设是基于初步的 工作中，观察到脂肪氧化在肌肉中被抑制 肥胖者与氧化酶降低有关 活动。这些初步数据构成了工作假说的基础 肥胖症患者骨骼肌中脂质氧化受到抑制 促进脂肪储存。第二个假设是减肥不会 增强脂肪氧化，但减少肌肉甘油三酯的储存 替代机制。第三种假设是运动训练 逆转了肥胖所带来的最初的脂质氧化减少， 促进脂肪利用。为了检验这些假设，需要确定以下几点： 特定目的I-如果骨骼吸收后脂代谢受损 肥胖者的肌肉以促进积累的方式 脂类；特异靶II--如果吸收后脂类代谢受损 在肥胖个体的骨骼肌中被纠正或补偿 与减肥和；特定目标III-如果运动训练增强 肥胖者吸收后脂质代谢与细胞 负责的机制。由于知之甚少，这些发现将是重要的。 关于脂代谢缺陷的机制， 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.