Protein and amino acid metabolism in malnutrition and metabolic stress

营养不良是全世界最普遍的营养问题，并且经常因感染而复杂化。炎症和免疫系统的激活都是对组织损伤和感染的正常反应，导致1）谷胱甘肽（GSH）的合成增加以平衡自由基的产生增加，和2）急性期蛋白的合成增加。这两种反应都导致对可能稀少的氨基酸供应的需求增加。在营养不良期间，这些反应可能进一步损害生长，并且可能自身受到损害，从而加强营养不良/感染的恶性循环。 我们的稳定同位素技术来测量GSH和单个血浆蛋白的合成，可以全面检查单个蛋白质或氨基酸产物在营养不良和/或氧化应激状态下如何受到影响的机制。我们已经开发了结肠炎或肠道炎症的仔猪模型，并且已经表明炎症确实损害肌肉中的生长和蛋白质合成，同时增加血浆蛋白的合成作为急性期反应的一部分。我们进一步表明，保持营养状态，而不是吃得少，不仅适应结肠炎的急性期反应，而且增加肌肉蛋白质合成，减轻结肠损伤的严重程度。 继续这一主题，我们正在研究蛋白质和/或锌缺乏的更具体的影响。我们的目标是将我们的蛋白质合成信息与锌动力学、GI病理生理学和促炎细胞因子反应相结合，以构建营养不良/炎症协同作用的更综合的解释。第二个主题是对生长因子如何刺激（以及挑战如何影响）肠道修复和刺激蛋白质和GSH合成的新的创新研究。结果预计将显示如何适应营养不良的影响，并强调饮食和营养状况的重要性，在安装有效应对压力。

Malnutrition is the most prevalent nutritional problem worldwide, and is frequently complicated by infections. Inflammation and activation of the immune system, which are both normal responses to tissue injury and infection, result in 1) increased synthesis of glutathione (GSH) to balance the increased production of free radicals, and 2) increased synthesis of acute phase proteins. Both responses result in increased demands for a potentially meagre supply of amino acids. During malnutrition these responses may further compromise growth and may be compromised themselves to potentiate the malnutrition/infection vicious cycle.     Our stable isotope techniques to measure synthesis of GSH and individual plasma proteins allow comprehensive examination of the mechanisms of how pools of individual proteins or products of amino acids are affected in states of malnutrition and/or oxidative stress. We have developed a piglet model of colitis or inflammation of the gut, and have shown that inflammation does compromise growth and protein synthesis in muscle while increasing synthesis of plasma proteins as part of the acute phase response. We have shown further that maintaining nutritional status, as opposed to eating less, not only accommodates the acute phase response of colitis, but increases muscle protein synthesis and lessens severity of the damage to the colon.     Continuing this theme, we are investigating the more specific effects of protein and/or zinc deficiency. We aim to integrate our protein synthesis information with zinc kinetics, GI pathophysiology and the pro-inflammatory cytokine response to construct a more integrative explanation of the malnutrition/ inflammation synergy. The second theme is a new and innovative investigation of how growth factors may stimulate (and how challenges may compromise) repair of the intestine and stimulate protein and GSH synthesis. Results are expected to show HOW adaptations to malnutrition are affected, and to underscore the importance of diet and nutritional status in mounting effective responses to stresses.