# REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $605,251

## Abstract

ABSTRACT
Most premature infants experience extrauterine growth restriction for reasons that are unclear and are at in-
creased lifelong risk for obesity and type 2 diabetes. Our long-term goal is to identify mechanisms that diminish
lean growth and alter metabolic responses to nutrition in preterm infants; these findings will inform the develop-
ment of new nutritional strategies to improve outcomes. The objective of this application is to determine if per-
sistence of the anabolic resistance to feeding following premature birth impairs lean growth and if specific amino
acid supplementation ameliorates lean mass accretion. The central hypothesis is that prematurity limits lean
growth by blunting amino acid- and insulin-induced stimulation of protein synthesis and myonuclear accretion in
skeletal muscle but can be improved by amino acid supplementation targeted to promote mechanistic target of
rapamycin complex 1 (mTORC1)-dependent cellular processes. The hypothesis is based on data from the ap-
plicants’ laboratories and supported by the literature. The rationale is that understanding the fundamental mech-
anisms by which prematurity alters the anabolic response to nutrition is essential to inform and modify feeding
practices for preterm infants to sustain intrauterine growth rates of lean mass after they are born. The hypothesis
will be tested by pursuing two specific aims: 1) Determine if the acute protein anabolic resistance to feeding in
the preterm is sustained long-term and results in reduced muscle and lean mass accretion; and 2) Determine if
supplementation with leucine and/or the arginine precursor, citrulline enhances lean growth by upregulating
mTORC1-dependent muscle protein synthesis and myonuclear accretion. When pigs born preterm and term
reach ages equivalent to human late-infancy or late-childhood, we will determine body composition, growth rate,
energy expenditure, hormone, substrate and metabolite profiles, and skeletal muscle protein synthesis and deg-
radation rates, blood flow, amino acid, insulin and eNOS signaling, metabolomic and transcriptomic profiles, and
satellite cell abundance and proliferation in response to feeding, pancreatic-substrate clamps, and supplemen-
tation with leucine and/or citrulline. The methods are established in the applicants’ laboratories. The approach is
innovative because it will use comprehensive approaches that will examine concurrently in vivo responses to
preterm birth of the principal processes that regulate muscle growth, i.e., protein synthesis, protein degradation,
and myonuclear accretion, and how these processes respond to dietary interventions targeted to promote anab-
olism. The proposed studies are unique because they comprehensively examine in a relevant preterm model
the mechanisms that underlie the anabolic resistance of the premature which limits lean growth and examine
the effectiveness of targeted amino acid supplementation on processes that regulate skeletal muscle growth.
T...

## Key facts

- **NIH application ID:** 10917256
- **Project number:** 5R01HD085573-24
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** TERESA A DAVIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $605,251
- **Award type:** 5
- **Project period:** 2016-04-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917256

## Citation

> US National Institutes of Health, RePORTER application 10917256, REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS (5R01HD085573-24). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10917256. Licensed CC0.

---

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