Effects of sex and adiposity on muscle protein synthesis

性别和肥胖对肌肉蛋白质合成的影响

• 批准号: 7037663
• 负责人: Bettina Mittendorfer
• 金额: $ 31.18万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-13 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037663
• 关键词: SDS polyacrylamide gel electrophoresis; binding proteins; body composition; clinical research; exercise; fasting; gender difference; human subject; magnetic resonance imaging; muscle proteins; obesity; phosphorylation; photon absorptiometry; protein biosynthesis; sex hormones; striated muscles; transmission electron microscopy

DESCRIPTION (provided by applicant): Adequate muscle mass is important for normal physical function and whole-body intermediary metabolism (including fuel metabolism). Men have more muscle mass than women, and obese people have a greater than expected muscle mass for their height (compared to lean individuals). However, this increase in muscle mass is less in women than in men. In contrast, loss of muscle mass during fasting or chronic underfeeding is greater in men and lean persons than in women and obese persons. The mechanisms responsible for these differences in muscle mass regulation during anabolic and catabolic conditions are not known. The main purpose of the proposed studies is to determine the effects of sex and adiposity on changes in skeletal muscle protein synthesis (MPS) in response to the major physiological conditions that stimulate (i.e., increased amino acid availability and resistance exercise) or inhibit (i.e., fasting) MPS. We anticipate that differences in muscle protein metabolism between men and women, and lean and obese individuals, that may be subtle or undetectable during basal conditions at rest, may become more apparent during those physiological conditions. We hypothesize that the amino acid- and exercise-induced stimulation of MPS is greater in men than women and that increased adiposity augments these responses both in men and women. However, during catabolic conditions the attenuation of MPS is greater in men than women and increased adiposity diminishes the fasting-induced reduction of MPS. Furthermore, we hypothesize that the differences between men and women are, in part, due to the presence of female sex-hormones. These hypotheses will be tested by evaluating MPS and the activity of intracellular factors that regulate protein synthesis in human subjects during 1) basal resting conditions, 2) during amino acid infusion, 3) after resistance leg exercise, and 4) after prolonged fasting, by using stable isotope labeled amino acid tracer infusion and assessment of the phosphorylation of key intracellular factors involved in the regulation of protein synthesis. The knowledge obtained from these studies will increase our understanding of the interactions between a person's sex and adiposity and the intracellular factors involved in protein synthesis and the regulation of MPS (and therefore muscle mass). This information should prove useful in developing novel therapeutic approaches aimed at maintaining muscle mass throughout a person's lifespan and in patients with conditions associated with muscle wasting.

描述（由申请人提供）：足够的肌肉质量对于正常的身体功能和全身中间代谢（包括燃料代谢）很重要。男性的肌肉质量比女性多，肥胖的人的身高比预期的肌肉质量要大（与瘦人相比）。但是，女性的肌肉质量的增加比男性少。相比之下，在禁食或慢性喂养过程中，肌肉质量的损失比女性和肥胖者更大。在合成代谢和分解代谢条件下肌肉质量调节的这些差异的机制尚不清楚。拟议研究的主要目的是确定性别和肥胖对骨骼肌肉蛋白合成（MPS）变化的影响，以响应刺激刺激（即增加氨基酸的可用性和耐药性）或抑制（即禁食）MPS的主要生理条件（即增加）。我们预计，在静止状态下，在基础条件下可能是微妙或无法检测到的男性和女性肌肉蛋白质代谢的差异，在这些生理条件下可能会变得更加明显。我们假设男性的氨基酸和运动引起的MP刺激要大于女性，并且增加肥胖增强了男性和女性的这些反应。但是，在分解代谢条件下，男性的MPS衰减比女性大，并且肥胖增加会减少禁食引起的MPS的减少。此外，我们假设男女之间的差异部分是由于存在女性性激素。这些假设将通过评估MPS和细胞内因子的活性来测试，这些因素在1）基础静止条件下调节人类受试者的蛋白质合成，2）在氨基酸输注期间，3）耐药性腿部运动后和4）在延长禁食后，通过使用稳定的同位素同位素标记的同型同位素的氨基酸液化和评估量的键入量的键入量，以弥补氨基酸的评估。 合成。从这些研究中获得的知识将增加我们对人的性别与肥胖之间的相互作用以及涉及蛋白质合成的细胞内因素以及MPS（因此肌肉质量）的调节的理解。该信息应证明对开发旨在在整个人的寿命以及与肌肉浪费有关的疾病的患者中保持旨在维持肌肉质量的新型治疗方法非常有用。