Regulation of Neonatal Muscle Protein Synthesis

新生儿肌肉蛋白合成的调节

基本信息

批准号：
9262972
负责人：
TERESA A DAVIS
金额：
$ 45.29万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-15 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9262972
关键词：
Adult Age Alanine Amino Acids Attenuated Basic Science Body Composition Bolus Infusion Branched-Chain Amino Acids Cell Proliferation Cell division Closure by clamp Complex Conceptions Continuous Infusion Data Effectiveness Enteral Enteral Feeding Enteral Nutrition Exhibits FRAP1 gene Family suidae Fatty acid glycerol esters Feeds Gestational Age Goals Growth Health Hormones Hospitals Human Individual Infant Infusion procedures Insulin Knowledge Laboratories Leucine Life Metabolic Metabolic syndrome Methods Mission Modality Modeling Muscle Muscle Proteins Muscle satellite cell Neonatal Nutrient Nutritional Nutritional Support Obesity Outcome Pancreas Parenteral Nutrition Pattern Periodicity Physiologic pulse Premature Birth Premature Infant Process Protein Biosynthesis Proteins Public Health Publishing Regimen Regulation Research Resistance Risk Schedule Signal Pathway Signal Transduction Skeletal Muscle Small for Gestational Age Infant Stimulus Supplementation Testing Thinness Transcript Translating Translation Initiation United States National Institutes of Health Weight Work base cost experience feeding glucose metabolism improved indexing innovation insulin sensitivity insulin signaling metabolomics muscle form neonate novel nutrition obesity risk premature prevent protein degradation public health relevance response satellite cell transcriptome

项目摘要

DESCRIPTION (provided by applicant): Most premature infants have experienced extrauterine growth restriction by hospital discharge. Many remain small to adulthood and incur short- and long-term costs to their metabolic health, including an increased risk for obesity. Our long-term goal is to identify strategies to optimize the nutritional management of premature infants. The objective of this application is to determine whether prematurity limits the anabolic response to feeding and if this is mitigated by optimizing feeding strategies to enhance the efficiency of nutrient use for anabolic processes. The central hypothesis is that prematurity reduces lean growth, particularly in small for gestational age (SGA) neonates, but lean growth can be improved by cyclical stimulation of mammalian target of rapamycin signaling imparted by either feeding on an intermittent bolus schedule, rather than continuously, or by ad- ministration of intermittent leucine pulses when continuous feeding must be prescribed. The hypothesis is based on data from the applicants' laboratories. The rationale is that understanding the fundamental mechanisms by which different modes of feeding modulate lean mass in early life has the potential to translate into practices that will improve lean growth of preterm infants. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Determine if prematurity alters the protein synthetic response of muscle to feeding by blunting insulin- and amino acid-induced translation initiation; 2) Determine if lean growth is reduced in the preterm, particularly SGA, but is improved by intermittent bolus feeding rather than continuous feeding delivered either parenterally or enterally; and 3) Determine if intermittent leucine pulses enhance lean growth by stimulating protein synthesis and myonuclear accretion and reducing degradation in pre- term continuously fed neonates. We will determine body composition, growth rate, and muscle protein synthesis and degradation, satellite cell abundance and proliferation, amino acid and insulin signaling, metabolite and whole transcriptome profiles, and insulin and amino acid sensitivity in SGA preterm, appropriate for gestational age (AGA) preterm, and term pigs fed on an intermittent bolus schedule or continuously, either parenterally or enterally, and in those provided intermittent leucine pulses when continuously fed. The methods are established in the applicants' laboratories. The approach is innovative because it will examine in the preterm piglet model the coordinated response of muscle protein synthesis, degradation, myonuclear accretion, amino acid and insulin signaling, and metabolite and transcript profiles that regulate lean growth. The proposed work is unique because it is the first to comprehensively examine in a relevant preterm model the effectiveness of different feeding modalities including a novel leucine supplementation approach on component processes that determine muscle growth. The proposed research is significant because it is expected to advance our under- standing of how prematurity impacts the anabolic response to nutrition. The results will provide important novel information required for the optimization of the nutritional management of preterm infants.

描述（由申请人提供）：大多数早产儿在出院时都经历过宫外生长受限，许多人到成年后仍然很小，并对其代谢健康造成短期和长期损失，包括肥胖风险增加。该应用的目的是确定优化早产儿营养管理的策略，以确定早产是否限制了喂养的合成代谢反应，以及是否可以通过优化喂养策略来减轻这种反应，以提高营养利用的效率。核心假设是，早产会降低瘦肉生长，特别是对于小于胎龄 (SGA) 的新生儿，但通过间歇性推注喂养或间歇性推注喂养来周期性刺激哺乳动物雷帕霉素靶标，可以改善瘦肉生长。连续喂养，或在必须规定连续喂养时间歇给予亮氨酸脉冲。该假设基于申请人实验室的数据。其基本原理是理解基本原理。不同喂养方式在生命早期调节瘦肉量的机制有可能转化为改善早产儿瘦肉生长的实践。在强有力的初步数据的指导下，这一假设将通过追求三个具体目标进行检验：1）确定是否。早产通过减弱胰岛素和氨基酸诱导的翻译起始来改变肌肉对喂养的蛋白质合成反应 2) 确定早产儿的瘦肉生长是否减少，特别是 SGA，但通过间歇性推注喂养而不是连续喂养而得到改善；肠外或肠内给药；以及 3) 确定间歇性亮氨酸脉冲是否通过刺激蛋白质合成和肌核增生并减少早产儿持续喂养的降解来促进瘦肉生长。、卫星细胞丰度和增殖、氨基酸和胰岛素信号传导、代谢物和全转录组谱以及 SGA 早产儿的胰岛素和氨基酸敏感性，适合胎龄 (AGA) 早产儿和足月这些方法是在申请人的实验室中建立的，因为它将在早产仔猪模型中检查。这项工作是独一无二的，因为它是第一个在相关领域进行全面研究的工作。早产儿模型不同喂养方式的有效性，包括一种新的亮氨酸补充方法对决定肌肉生长的组成过程的影响，这项研究意义重大，因为它有望促进我们对早产如何影响营养的合成代谢反应的理解。提供优化早产儿营养管理所需的重要新颖信息。