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

• 批准号: 8547087
• 负责人: TERESA A DAVIS
• 金额: $ 32.85万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/8547087
• 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

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.

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，但许多人的经历都会流动，这可能会在代谢健康和生产力方面造成短期和长期成本。我们的长期目标是确定优化人类婴儿和年轻猪的营养管理的策略。该应用的目的是确定在蛋白质和/或能量的摄入量时，是否可以使用口服亮氨酸补充剂来增强早期生长。中心假设是，补充亮氨酸刺激了调节蛋白质合成和卫星细胞复制的信号传导途径，并抑制早期蛋白质降解， 从长远来看，这些影响会增强瘦长的生长。该假设基于申请人实验室的数据。理由是，了解亮氨酸在早期生命中调节瘦体重的基本机制有可能转化为可以改善低出生体重婴儿和 早期断奶小猪。在强大的初步数据的指导下，将通过追求两个具体目的来检验该假设：1）确定长时间的亮氨酸补充边缘蛋白饮食是否通过上调蛋白质的合成和肌核积聚和肌核蛋白质素来增强质量，并降解蛋白质，并确定此反应是否需要其他分支酸的酸性酸性酸化; 2）确定饮食中对蛋白质和能量略有限制的饮食中补充亮氨酸，亮氨酸和其他支链氨基酸是否会增强瘦质量积聚，并确定所涉及的机制。我们将确定身体成分，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，氨基酸信号传导到翻译，降解信号传导和喂食10 d亮氨酸或分支链氨基酸氨基酸含量的年轻猪中的年轻猪氧化（量）（80％）（80％）（蛋白质）。这些方法在申请人的实验室中建立了良好的。该方法具有创新性，因为它将检查肌肉蛋白质合成，蛋白质降解和肌能积聚的协调反应，并在早期生活中补充长期亮氨酸，并确定对瘦长的影响。拟议的工作是独一无二的，因为它是第一个全面检查确定肌肉生长的所有组件过程的协调调节。拟议的研究非常重要，因为预计它将促进我们对亮氨酸在早期生命中瘦长增长中的作用的理解。结果将提供有关使用补充亮氨酸来优化低出生体重婴儿的营养管理的重要新信息，并提高饮食中营养素用于猪肉生产的效率。