Nutritional Stimulation of Muscle Protein Synthesis

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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.