Nutritional Stimulation of Muscle Protein Synthesis

本项目的目的是研究运动和营养在促进严重烧伤恢复期儿童肌肉合成代谢中的作用。我们的主要终点将是净肌肉蛋白质合成率，这是增加肌肉大小和力量的代谢基础。根据我们对健康正常成年志愿者的经验，我们的一般假设是运动、氨基酸和胰岛素都促进净肌蛋白的合成。我们认为运动提高了蛋白质合成过程的效率，而摄入的氨基酸刺激了酸的运输，从而为合成提供了前体。我们认为胰岛素在刺激合成方面的作用机制与运动相似，但运动后胰岛素的作用主要是防止运动后肌肉蛋白质分解的增加。具体来说，我们将探讨以下假设在儿童从严重烧伤恢复：1。运动、摄入的氨基酸和摄入的碳水化合物都会刺激肌肉蛋白质的合成。2. 休息时摄入碳水化合物会增强摄入的氨基酸对肌肉蛋白质合成的影响。3. 摄入的氨基酸对肌肉蛋白质合成的刺激作用会被先前的运动放大。4. 运动后摄入碳水化合物可以防止运动后肌肉蛋白质分解的增加。5. 运动后摄入碳水化合物加氨基酸会刺激肌肉蛋白质合成，抑制蛋白质分解，从而通过两种机制放大对运动的合成代谢反应。6. 尽管运动训练可能会减少肌肉蛋白质转换（即合成和分解）对单次运动的反应，但运动后摄入的氨基酸仍比训练后休息时摄入的氨基酸更能促进净肌肉蛋白质的合成，因为合成过程的效率提高了。7. 碳水化合物的摄入会抑制训练有素的儿童运动后肌肉蛋白质的分解。8. 经过训练的儿童在运动后摄入碳水化合物和氨基酸会通过刺激肌肉蛋白质合成和抑制肌肉蛋白质分解来增强对运动的合成代谢反应。肌肉蛋白动力学将使用稳定同位素示踪方法、动静脉取样和肌肉活检来确定。这些研究的结果将导致一项干预性研究的设计，其中将调查最佳营养补充剂的长期影响。

It is the goal of this project to investigate the effects of exercise and nutrition in promoting muscle anabolism in children recovering from severe burn injury. Our primary endpoint will be the rate of net muscle protein synthesis, which is the metabolic basis for increased muscle size and strength. Based on our experience in healthy normal adult volunteers, our general hypothesis is that exercise, amino acids and insulin all promote net muscle protein synthesis. We propose that exercise increases the efficiency of the protein synthetic process, while ingested amino acids stimulate acid transport, thereby providing precursors for synthesis. We propose that at result insulin functions by similar mechanisms as exercise with regard to stimulating synthesis, but after exercise insulin functions primarily by preventing the increase in muscle protein breakdown that normally occurs after exercise. Specifically, we will investigate the following hypotheses in children recovering from severe burn injury: 1. Exercise, ingested amino acids, and ingested carbohydrate all stimulate muscle protein synthesis. 2. Ingestion of carbohydrate at rest will amplify the effects of ingested amino acids on muscle protein synthesis. 3. The stimulatory effect of ingested amino acids on muscle protein synthesis will be amplified by prior exercise. 4. Ingestion of carbohydrate after exercise will prevent the post-exercise increase in muscle protein breakdown that normally occurs. 5. Ingestion of carbohydrate plus amino acids after exercise will stimulate muscle protein synthesis and inhibit protein breakdown, thereby amplifying the anabolic response to exercise by two mechanisms. 6. Although exercise training may diminish the response of muscle protein turnover (i.e., synthesis and breakdown) to a single bout of exercise, the ingestion of amino acids after exercise nonetheless promotes net muscle protein synthesis to a greater extent than when given to trained children at rest because of the increased efficiency of the synthetic process. 7. Carbohydrate ingestion will inhibit muscle protein breakdown after exercise in trained children. 8. Carbohydrate plus amino acid ingested after exercise in trained children will amplify the anabolic response to exercise by both stimulating muscle protein synthesis and inhibiting muscle protein breakdown. Muscle protein kinetics will be determined using stable isotope tracer methodology and arterial-venous sampling and muscle biopsies. The results of these studies should lead to the design of an interventional study in which the long-term effects of an optimal nutritional supplement will be investigated.