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

我的研究计划的长期目标是阐明饮食蛋白质发挥其生物效应的作用和机制，但这项建议的主要重点是基于鳕鱼蛋白质的氨基酸含量。我们之前的研究表明，鳕鱼蛋白对血脂、胰岛素敏感性和骨骼肌恢复都有有益的影响。此外，我们观察到鳕鱼蛋白对肌肉再生的有利作用部分依赖于其高含量的精氨酸、赖氨酸、甘氨酸和牛磺酸(ALGT)的抗炎和生肌作用。因此，在这一更新应用中，我建议进一步探索这些新的发现，并研究鳕鱼蛋白中大量存在的氨基酸影响损伤后骨骼肌再生的潜在机制。我建议研究鳕鱼蛋白提供的大量含硫氨基酸和丙氨酸，以补充ALGT对骨骼肌损伤后再生的有利作用。在活体方法中，大鼠将接受丙氨酸和蛋氨酸+胱氨酸单独治疗，并在损伤前和损伤后联合ALGT治疗，并将在一系列实验中测量以下内容：(A)与骨骼肌修复有关的炎症和转录因子，通过测量肌肉质量、肌肉纤维横截面积(µm2)和间质面积协调成肌诱导和分化的机制，炎症细胞聚集的时间进程，转录因子、MyoD和肌肉生成素的表达水平，(B)通过检测IGF-1、p-Akt、p-70S6K、Pax-7、Ki-67、Pax-7、Ki-67、(C)通过检测GSK-3和p-GSK-3、Atrogin-1和MURF-1来研究骨骼肌蛋白质降解的机制，以及(D)参与大鼠骨骼肌蛋白质降解的基因表达的变化。这些新颖的研究将产生关于氨基酸对损伤后炎症和肌肉再生的重要性的新知识，并将为鳕鱼蛋白及其生物活性成分作为功能食品的使用提供指导。

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.