Leucine and HMB Supplementation in Early Life to Promote Muscle Growth at the Expense of Adipose Deposition

生命早期补充亮氨酸和 HMB 可促进肌肉生长，但会减少脂肪沉积

基本信息

批准号：
10228667
负责人：
TERESA A DAVIS
金额：
$ 40.47万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10228667
关键词：
Adipose tissue Affect Age Agriculture Amino Acids Anabolic Agents Anabolism Animal Feed Basic Science Body Composition Body mass index Branched-Chain Amino Acids Cell Proliferation Chronic Data Deposition Diet Dietary Component Dietary Proteins Dietary intake Energy Intake Energy Metabolism Family suidae Fatty acid glycerol esters Goals Growth Health Health Food Hormones Human Infant Insulin Knowledge Laboratories Leucine Life Link Measures Metabolic Methods Mission Modeling Morbidity - disease rate Muscle Muscle Proteins Neonatal Newborn Infant Nutrient Nutritional Obesity Organism Outcome Pathway interactions Physiologic pulse Plasma Populations at Risk Process Production Productivity Protein Biosynthesis Proteins Protocols documentation Public Health Quality of life Recommendation Regulation Research Risk Role Signal Pathway Signal Transduction Skeletal Muscle Supplementation Testing Thinness Translating Translation Initiation Tube United States National Institutes of Health Weight Gain Work adult obesity adverse outcome base beta-hydroxyisovaleric acid cost detection of nutrient dietary dietary guidelines energy balance feeding improved infancy innovation lean body mass metabolic rate muscle form novel nutrition obesity in children obesity risk overweight adults oxidation postnatal postnatal period prevent programs protein intake response satellite cell skeletal muscle growth

项目摘要

ABSTRACT The composition and rate of weight gain in infancy are highly sensitive to dietary intake. Excess adipose tissue gain in early infancy predisposes to childhood obesity and increases the risk for developing adult obesity that incurs short- and long-term costs in terms of metabolic health and productivity. Our long-term goal is to identify dietary strategies that can be translated to populations of at risk human infants and young pigs to promote dietary amino acid use in support of muscle growth at the expense of adipose deposition. The objective of this application is to determine whether supplementation of a complete diet (fed to meet requirements) with leucine or its metabolite β-hydroxy-β-methylbutyrate (HMB) will improve efficiency of protein utilization by stimulating the muscle's anabolic processes and thereby enhance the partitioning of dietary nutrients toward lean growth, while mitigating fat deposition. The central hypothesis is that in infancy, leucine or HMB supplementation stimulates the pathways in skeletal muscle that regulate protein synthesis and satellite cell replication and, thereby, enhance lean growth. When sustained long-term, the increased metabolic mass diminishes overall energy balance and fat accretion. The hypothesis is based on data from the applicants' laboratories. The rationale is that by understanding the mechanisms by which dietary components can influence muscle growth in early infancy and, in turn, impact dietary energy utilization, we can establish appropriate dietary guidelines to optimize the growth of lean mass whilst mitigating excess fat deposition. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine if feeding a complete diet that meets protein and energy requirements and supplemented with leucine enhances muscle accretion by up-regulating protein synthesis and myonuclear accretion, and whether the resulting change in metabolic mass reduces energy available for fat accretion. 2) Determine if HMB supplementation of a complete diet utilizes nutrient sensing pathways similar to leucine to enhance muscle and lean mass accretion, and mitigate fat deposition. Using methods established in the applicants' laboratories, responses in growth rate, body composition, the efficiency of dietary protein and energy use for growth, energy expenditure, protein synthesis rates, nutrient signaling, satellite cell abundance and proliferation, and hormone, substrate, and metabolite profiles will be measured in young pigs over 3 weeks. The approach is innovative because it will identify how the cellular responses of muscle to long-term leucine and HMB supplementation impact whole body protein and energy utilization to influence growth and the composition of weight gain. The proposed research is significant because it is expected to advance our basic understanding of both the role of leucine and its metabolite in the regulation of muscle growth in early life, and the significance of skeletal muscle for the overall energy and protein economy of the growing organism. Novel information will be gained on the potential for using leucine and HMB supplementation to promote lean growth and mitigate fat accretion in infants and for pork production.

抽象的婴儿期的体重增加速率对饮食摄入高度敏感。脂肪组织过多在婴儿早期易患儿童肥胖症，增加了成年肥胖的风险就代谢健康和生产率而言，短期和长期成本会产生。我们的长期目标是确定可以转化为人类婴儿和年轻猪的饮食策略，以促进饮食中的氨基酸用于支持肌肉生长以脂肪沉积为代价。这个目的应用是确定是否补充了亮氨酸的完整饮食（满足要求）或其代谢物β-羟基-β-甲基丁酸（HMB）将通过刺激来提高蛋白质利用的效率肌肉的合成代谢过程，从而增强了饮食营养成分的分配，同时减轻脂肪沉积。中心假设是在婴儿期，亮氨酸或HMB补充刺激调节蛋白质合成和卫星细胞复制的骨骼肌的途径，以及从而增强瘦长的增长。长期持续持续，代谢质量增加会减少总体能量平衡和脂肪积聚。该假设基于申请人实验室的数据。理由是，通过了解饮食成分可以影响肌肉生长的机制在婴儿期的早期，进而影响饮食能源利用率，我们可以建立适当的饮食指南优化瘦质量的生长，同时减轻多余的脂肪沉积。在强大的初步数据的指导下，该假设将通过追求两个具体目的来检验：1）确定是否喂养满足的完整饮食蛋白质和能量需求，并通过上调来补充亮氨酸增强肌肉积聚蛋白质合成和肌核积聚，以及代谢质量的变化是否会减少可用于脂肪积聚的能量。 2）确定补充HMB是否利用营养素感测与亮氨酸相似的途径，以增强肌肉和瘦肉积聚，并减轻脂肪沉积。使用申请人实验室中建立的方法，增长率的响应，身体成分，饮食蛋白质和能量用途的效率，用于生长，能量消耗，蛋白质合成速率，营养素信号传导，卫星细胞丰度和增殖，以及骑马，底物和代谢物轮廓将是在3周内在幼猪中测量。该方法具有创新性，因为它将确定细胞的方式肌肉对长期亮氨酸和HMB补充的反应会影响全身蛋白质和能量利用来影响生长和体重增加的组成。拟议的研究很重要因为期望它可以提高我们对亮氨酸及其代谢物在中的作用的基本理解调节早期肌肉生长以及骨骼肌对整体能量的重要性生长生物体的蛋白质经济。新的信息将获得使用亮氨酸的潜力并补充HMB，以促进婴儿和猪肉生产的瘦肉生长和减轻脂肪囊泡。