Leucine Supplementation to Promote Lean Growth in Early Life

补充亮氨酸促进生命早期的精益生长

基本信息

批准号：
8334836
负责人：
TERESA A DAVIS
金额：
$ 35.86万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-20 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8334836
关键词：
Adult Amino Acids Animals Basic Science Body Composition Branched-Chain Amino Acids Cell Proliferation Clinical Complex Consumption Data Desire for food Diet Eating Family suidae Feeds Goals Growth Health Health Food Human Infant Insulin Insulin Signaling Pathway Intake Knowledge Laboratories Lead Leucine Life Low Birth Weight Infant Metabolic Methods Mission Modeling Morbidity - disease rate Muscle Muscle Proteins Neonatal Nutrient Nutritional Nutritional Support Oral Outcome Process Production Productivity Protein Biosynthesis Proteins Public Health Publishing Regulation Research Role Signal Pathway Signal Transduction Supplementation Testing Translating Translation Initiation Translations United States National Institutes of Health Weaning Work base cost dietary restriction dietary supplements experience falls feeding improved innovation mTOR protein meetings neonate novel oxidation prevent protein degradation protein intake response satellite cell

项目摘要

DESCRIPTION (provided by applicant): Despite improvements in the nutritional management of low birth weight infants and early weaned pigs, many experience growth faltering and this can incur both short- and long-term costs in terms of metabolic health and productivity. Our long-term goal is to identify strategies to optimize the nutritional management of both the human infant and the young pig whose growth has been compromised. The objective of this application is to determine whether the use of an oral leucine supplement can be used to enhance lean growth in early life when the intakes of protein and/or energy are marginal. The central hypothesis is that leucine supplementation stimulates the signaling pathways that regulate protein synthesis and satellite cell replication and inhibit protein degradation during early life, and these effects enhance lean growth when sustained over the long-term. The hypothesis is based on data from the applicants' laboratories. The rationale is that understanding the fundamental mechanisms by which leucine modulates lean body mass during early life has the potential to translate into practices that will improve lean growth of low birth weight infants and early weaned piglets. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine whether prolonged leucine supplementation of a marginal protein diet enhances lean mass by up-regulating protein synthesis and myonuclear accretion and down-regulating protein degradation, and also determine whether this response requires the addition of other branched-chain amino acids; and 2) Determine if supplementation with leucine, or leucine and additional branched chain amino acids, of a diet that is marginally restricted in both protein and energy will enhance lean mass accretion, and to identify the mechanisms involved. We will determine body composition, growth rate, feed efficiency, protein synthesis and degradation rates, satellite cell abundance and proliferative capacity, amino acid signaling to translation, degradation signaling, and amino acid oxidation in young pigs fed for 10 d leucine or branched-chain amino acid supplemented diets that are marginally (80%) restricted in protein (Aim 1) or protein and energy (Aim 2). The methods are well-established in the applicants' laboratories. The approach is innovative, because it will examine the coordinated response of muscle protein synthesis, protein degradation, and myonuclear accretion to long-term leucine supplementation during early life and determine the impact on lean growth. The proposed work is unique because it is the first to comprehensively examine the coordinated regulation of all the component processes that determine muscle growth. The proposed research is significant, because it is expected to advance our understanding of the role of leucine in the regulation of lean growth in early life. The results will provide important novel information on the potential for using leucine supplementation to optimize the nutritional management of low birth weight infants, and to improve the efficiency of utilization of dietary nutrients for pork production. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because the discovery of the mechanisms by which leucine influences lean growth in neonates is expected to bring basic research closer to the translational level of improving the nutritional support of low birth weight infants as well as the efficiency of utilization of dietary nutrients fr pork production. Thus, the proposed research using an agriculturally important domestic species is relevant to the missions of the NIH and USDA as it will provide fundamental new knowledge that has dual benefits relevant for the improvement of human health and food animal production.

描述（由申请人提供）：尽管低出生体重婴儿和早期断奶猪的营养管理有所改善，但许多猪的生长缓慢，这可能会在代谢健康和生产力方面产生短期和长期成本。我们的长期目标是找到优化人类婴儿和生长受到损害的仔猪营养管理的策略。本申请的目的是确定当蛋白质和/或能量的摄入量很少时，是否可以使用口服亮氨酸补充剂来增强生命早期的瘦肉生长。中心假设是亮氨酸补充会刺激调节蛋白质合成和卫星细胞复制的信号通路，并抑制生命早期的蛋白质降解，如果这些效应长期持续下去，就会增强瘦肉生长。该假设基于申请人实验室的数据。其基本原理是，了解亮氨酸在生命早期调节瘦体重的基本机制有可能转化为改善低出生体重婴儿瘦体重生长的实践，以及早期断奶仔猪。在强有力的初步数据的指导下，这一假设将通过追求两个具体目标进行检验：1）确定边缘蛋白质饮食中长期补充亮氨酸是否可以通过上调蛋白质合成和肌核增生以及下调蛋白质降解来增强瘦体重，以及确定该反应是否需要添加其他支链氨基酸； 2) 确定在蛋白质和能量均受到轻微限制的饮食中补充亮氨酸或亮氨酸和其他支链氨基酸是否会增强瘦体重增加，并确定所涉及的机制。我们将测定饲喂 10 天亮氨酸或支链的幼猪的身体成分、生长速率、饲料效率、蛋白质合成和降解速率、卫星细胞丰度和增殖能力、翻译氨基酸信号传导、降解信号传导和氨基酸氧化补充氨基酸的饮食略微（80%）限制蛋白质（目标 1）或蛋白质和能量（目标 2）。这些方法已在申请人的实验室中得到完善。该方法具有创新性，因为它将检查肌肉蛋白质合成、蛋白质降解和肌核增生对生命早期长期补充亮氨酸的协调反应，并确定对瘦肉生长的影响。这项工作是独一无二的，因为它是第一个全面检查决定肌肉生长的所有组成过程的协调调节的工作。这项研究意义重大，因为它有望增进我们对亮氨酸在生命早期瘦肉生长调节中作用的理解。研究结果将为利用亮氨酸补充剂优化低出生体重婴儿的营养管理以及提高猪肉生产中膳食营养素的利用效率提供重要的新信息。公共健康相关性：拟议的研究与公共健康相关，因为亮氨酸影响新生儿瘦肉生长的机制的发现有望使基础研究更接近改善低出生体重婴儿营养支持的转化水平以及猪肉生产中日粮营养素的利用效率。因此，拟议的使用农业上重要的家养物种的研究与美国国立卫生研究院和美国农业部的使命相关，因为它将提供具有与改善人类健康和食用动物生产相关的双重效益的基本新知识。