NITROGEN METABOLISM IN GROWTH RESTRICTED NEONATES

生长受限新生儿的氮代谢

• 批准号: 7374320
• 负责人: PATTI THUREEN
• 金额: $ 10.85万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-24 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374320
• 关键词: balance; bioenergetics; biotransformation; body composition; calorimetry; disease /disorder proneness /risk; embryo /fetus; gestational age; glucose; glycerol; growth /development; hypertension; insulin sensitivity /resistance; leucine; measurement; metabolism; nitrogen metabolism; oxidation; prenatal growth disorder; protein metabolism; proteins; water

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fetal growth restriction may produce life-long alterations in growth and development as well as increase the risk of diseases in adulthood such as diabetes, insulin resistance and hypertension. It is not known if an aggressive feeding approach early in life might improve outcome in the severely growth restricted infant, particularly of early growth. This first requires understanding the specifics of abnormal nutrient metabolism and the qualitative and quantitative responses to feeding in these infants. We hypothesize that preterm SGA infants who had intrauterine growth restriction (IUGR) demonstrate abnormal nitrogen metabolism consisting of decreased rates of protein synthesis, oxidation and catabolism compared with AGA infants. Previous studies of nutrient metabolism have not shown consistently different metabolic patterns between SGA and AGA infants, probably because the SGA infants were not uniformly growth restricted. We will resolve this by studying a subgroup of SGA infants that are known to be IUGR based on fetal studies that demonstrate markedly restricted rates of in utero growth. We then will test our hypothesis using tracer leucine kinetic measurements to quantify protein metabolism in studies performed at the end of day 1, week 1 and month 1 of postnatal life, with both AGA and IUGR infants matched for gestational age and relatively high nutrient intake. In addition, we will determine energy expenditure by both indirect calorimetry and doubly labeled water techniques, glucose and glycerol turnover rates using tracer methodology, changes in body composition, and nutrient balance using our established techniques. This study will be the first comprehensive study of changes in protein metabolism, body composition and growth in IUGR infants receiving aggressive nutrient intakes over an extended period of time, and will definitively determine if there are significant nutritional metabolic differences in IUGR versus AGA infants by uniquely identifying the infants who demonstrate the extreme of abnormal intrauterine growth rate. The results of these studies could alter current feeding practices and provide a rational basis for future nutritional intervention studies in severely growth restricted infants.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。胎儿生长受限可能导致终生的生长发育改变，并增加成年后患糖尿病、胰岛素抵抗和高血压等疾病的风险。目前尚不清楚早期积极的喂养方法是否可以改善严重生长受限婴儿的结局，特别是早期生长受限婴儿。这首先需要了解异常营养代谢的具体情况以及这些婴儿对喂养的定性和定量反应。我们假设，与AGA婴儿相比，患有宫内生长受限（IUGR）的SGA早产儿表现出异常的氮代谢，包括蛋白质合成、氧化和分解代谢率下降。以前的营养代谢研究并没有显示出SGA和AGA婴儿的代谢模式有一致的不同，可能是因为SGA婴儿的生长并没有受到统一的限制。我们将通过研究一组已知为IUGR的SGA婴儿来解决这个问题，这些婴儿基于胎儿研究，表明子宫内生长速度明显受限。然后，我们将使用示踪亮氨酸动力学测量来验证我们的假设，以量化在出生后第1天、第1周和第1个月进行的研究中的蛋白质代谢，AGA和IUGR婴儿的胎龄和相对较高的营养摄入量相匹配。此外，我们将通过间接量热法和双标记水技术确定能量消耗，使用示踪剂方法确定葡萄糖和甘油周转率，使用我们已建立的技术确定身体成分的变化和营养平衡。本研究将首次全面研究长期摄入积极营养的IUGR婴儿的蛋白质代谢、身体组成和生长变化，并通过独特识别表现出极端异常宫内生长速率的婴儿，最终确定IUGR婴儿与AGA婴儿是否存在显著的营养代谢差异。这些研究的结果可以改变目前的喂养方式，并为未来对严重生长受限婴儿的营养干预研究提供合理的基础。