Effects of sex and adiposity on muscle protein synthesis

描述（由申请人提供）：充足的肌肉质量对正常的身体功能和全身中间代谢（包括燃料代谢）很重要。男性比女性拥有更多的肌肉质量，肥胖的人比他们身高的预期肌肉质量更大（与瘦的人相比）。然而，这种肌肉质量的增加在女性中比男性少。相比之下，在禁食或慢性喂养不足期间，男性和瘦人的肌肉质量损失大于女性和肥胖者。合成代谢和分解代谢条件下肌肉质量调节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蛋白质合成（MPS）变化的影响，以响应刺激（即，增加的氨基酸可用性和阻力运动）或抑制（即，空腹）MPS。我们预计，男性和女性之间的肌肉蛋白质代谢的差异，以及瘦和肥胖的个人，这可能是微妙的或不可检测的基础条件下休息，可能会变得更加明显，在这些生理条件。我们假设，氨基酸和运动诱导的MPS刺激在男性中比女性更大，并且肥胖增加会增强男性和女性的这些反应。然而，在分解代谢条件下，MPS的衰减在男性中比女性更大，并且增加的肥胖减少了禁食诱导的MPS降低。此外，我们假设男性和女性之间的差异部分是由于女性性激素的存在。将通过评价MPS和调节人类受试者在1）基础静息条件下、2）氨基酸输注期间、3）阻力腿运动后和4）长时间禁食后蛋白质合成的细胞内因子的活性来检验这些假设，通过使用稳定同位素标记的氨基酸示踪剂输注和评估参与蛋白质调节的关键细胞内因子的磷酸化，合成.从这些研究中获得的知识将增加我们对一个人的性别和肥胖之间的相互作用以及参与蛋白质合成和MPS（因此肌肉质量）调节的细胞内因素的理解。这些信息应该证明在开发新的治疗方法，旨在保持肌肉质量在一个人的整个生命周期和患者与肌肉萎缩相关的条件是有用的。

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.