The role of dietary protein in skeletal muscle regeneration post-injury

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The long term goal of my research program is to elucidate the effects and mechanisms whereby dietary proteins exert their biological effects but the main focus of this proposal is based on the amino acid content of cod protein. Our previous studies have shown a beneficial impact of cod protein on plasma lipids, insulin sensitivity and skeletal muscle recovery. Further, we observed that the beneficial effect of cod protein on muscle regeneration relies partly on the anti-inflammatory and myogenic action of its high arginine, lysine, glycine and taurine (ALGT) content. In this renewal application, I therefore propose to further explore these novel findings and to study the underlying mechanism by which amino acids found in high amounts in cod protein influence skeletal muscle regeneration following an injury. I propose to study sulfur amino acids and alanine provided in high quantities by cod protein that could complement the beneficial effect of ALGT on regeneration of skeletal muscle following an injury. Using in vivo methods, rats will be treated with alanine and methionine+cystine alone, combined together and with ALGT prior and following an injury and the following will be measured in a series of experiments: (a) mechanisms related to skeletal muscle repair through inflammation and transcription factors which coordinate myogenic induction and differentiation by measuring muscle mass, muscle fiber cross-sectional area (µm2) and interstitial area, time course of inflammatory cell accumulation, expression level of transcription factors, MyoD and myogenin, (b) mechanisms of skeletal muscle protein synthesis by measuring IGF-1, p-Akt, p-70S6kinase, Pax-7, Ki-67, (c) mechanisms of skeletal muscle protein degradation by measuring GSK-3 & p-GSK-3, Atrogin-1 and MURF-1, and (d) changes in expression of genes involved in muscle protein degradation in rat skeletal muscle. These novel studies will generate new knowledge on the importance of amino acids on inflammation and muscle regeneration following an injury and will also provide guidance regarding the use of cod protein and its bioactive components as functional foods.