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：
9795011
负责人：
TERESA A DAVIS
金额：
$ 41.05万
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 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9795011
关键词：
Adipose tissue Adult 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 Morbidity - disease rate Muscle Muscle Proteins Neonatal Newborn Infant Nutrient Nutritional Obesity Organism Outcome Overweight 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 cost detection of nutrient dietary guidelines energy balance feeding human model improved infancy innovation lean body mass metabolic rate muscle form novel nutrition obesity in children obesity risk 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.

抽象的婴儿期体重增加的成分和速度对饮食摄入过量的脂肪组织高度敏感。婴儿早期体重增加容易导致儿童肥胖，并增加成年肥胖的风险，在代谢健康和生产力方面会产生短期和长期成本。我们的长期目标是确定。可应用于高危人类婴儿和幼猪群体的饮食策略，以促进使用膳食氨基酸来支持肌肉生长，但会减少脂肪沉积。应用是确定是否在完整饮食（喂养以满足要求）中补充亮氨酸或其代谢物β-羟基-β-甲基丁酸酯（HMB）将通过刺激提高蛋白质利用效率肌肉的合成代谢过程，从而增强膳食营养素对瘦肉生长的分配，核心假设是在婴儿期补充亮氨酸或 HMB。刺激骨骼肌中调节蛋白质合成和卫星细胞复制的途径，当长期持续时，增加的代谢量总体上会减少该假设基于申请人实验室的数据。基本原理是通过了解饮食成分影响肌肉生长的机制在婴儿早期，进而影响膳食能量利用，我们可以制定适当的膳食指南在强有力的初步数据的指导下，优化瘦体重的增长，同时减少多余的脂肪沉积。该假设将通过追求两个具体目标来检验：1）确定喂养完整饮食是否满足蛋白质和能量需求并补充亮氨酸通过上调增强肌肉加速蛋白质合成和肌核增生，以及由此产生的代谢量变化是否会减少 2) 确定完整饮食中的 HMB 补充是否利用了营养素。与亮氨酸类似的传感途径可增强肌肉和瘦肉质量加速，并减轻脂肪沉积。使用申请人实验室建立的方法，对生长速度、身体成分、膳食蛋白质和能量用于生长的效率、能量消耗、蛋白质合成率、营养素信号传导、卫星细胞丰度和增殖以及激素、底物和代谢物谱将被这种方法是创新的，因为它可以确定细胞如何变化。肌肉对长期补充亮氨酸和 HMB 的反应会影响全身蛋白质和能量拟议的研究意义重大因为它有望增进我们对亮氨酸及其代谢物在生命早期肌肉生长的调节，以及骨骼肌对于整体能量和能量的重要性将获得有关使用亮氨酸潜力的新信息。补充 HMB 可促进婴儿瘦肉生长并减少脂肪堆积以及猪肉生产。