Effects of sex and adiposity on muscle protein synthesis

描述(申请人提供)：足够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)非常重要。男性的肌肉质量比女性多，肥胖者的身高肌肉质量比预期的要大(与苗条的人相比)。然而，女性肌肉质量的增加要比男性少。相比之下，在禁食或慢性喂食不足期间，男性和瘦人的肌肉质量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。这项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)的影响，以响应刺激(即增加氨基酸可获得性和抵抗运动)或抑制(即禁食)MPS的主要生理条件。我们预计，男性和女性以及瘦肉者和肥胖者之间的肌肉蛋白质代谢差异，在休息的基础条件下可能是微妙的或无法检测到的，在这些生理条件下可能会变得更加明显。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，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，男性MPS的下降比女性更大，肥胖症的增加减少了禁食导致的MPS下降。此外，我们假设男性和女性之间的差异在一定程度上是由于女性性激素的存在。这些假说将通过评估MPS和调节人体蛋白质合成的细胞内因子的活性来验证，方法是：1)基础休息条件下，2)氨基酸输注期间，3)抗阻腿部运动后，4)长时间禁食后，使用稳定同位素标记的氨基酸示踪剂输注，以及评估参与蛋白质合成调节的关键细胞内因子的磷酸化。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，以及涉及蛋白质合成和MPS(从而肌肉质量)调节的细胞内因素的理解。这些信息应该被证明对开发新的治疗方法很有用，目的是在一个人的一生中保持肌肉质量，并用于与肌肉萎缩相关的疾病。

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.