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

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $412,917

## Abstract

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 ...

## Key facts

- **NIH application ID:** 10005440
- **Project number:** 5R01HD099080-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** TERESA A DAVIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,917
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005440

## Citation

> US National Institutes of Health, RePORTER application 10005440, Leucine and HMB Supplementation in Early Life to Promote Muscle Growth at the Expense of Adipose Deposition (5R01HD099080-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10005440. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*