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

• 批准号: 10005440
• 负责人: TERESA A DAVIS
• 金额: $ 41.29万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/10005440
• 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; Modeling; 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; beta-hydroxyisovaleric acid; cost; detection of nutrient; dietary guidelines; energy balance; feeding; 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

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 婴儿期体重增加的构成和速度对饮食摄入高度敏感。多余的脂肪组织 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，但会消耗脂肪沉积。此举的目的 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的分配，促进瘦肉生长， 同时减少脂肪沉积。中心假设是，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， 从而促进精益生长。当长期持续时，增加的代谢量总体上会减少 能量平衡和脂肪堆积。该假设基于申请人实验室的数据。这 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 优化瘦体重的增长，同时减少多余的脂肪沉积。在强有力的初步数据的指导下， 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增长 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 可用于脂肪堆积的能量。 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的增加，并减少脂肪沉积。 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 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 在 3 周内对幼猪进行测量。该方法具有创新性，因为它将确定细胞如何 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 利用影响生长和体重增加的组成。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 生长有机体的蛋白质经济。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。