Regulation of Skeletal Muscle Protein Synthesis in the Preterm Pig by Intermittent Leucine Pulses During Continuous Parenteral Feeding

Authors

Marko Rudar
Agus Suryawan
Hanh V Nguyen
Shaji K Chacko
Caitlin Vonderohe
Barbara Stoll
Douglas G Burrin
Marta L Fiorotto
Teresa A Davis

Publication Date

2-1-2023

Journal

Journal of Parenteral and Enteral Nutrition

DOI

10.1002/jpen.2450

PMID

36128996

PMCID

PMC10621874

PubMedCentral® Posted Date

2-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Infant, Newborn, Female, Humans, Animals, Swine, Leucine, Animals, Newborn, Premature Birth, Muscle, Skeletal, TOR Serine-Threonine Kinases, Mechanistic Target of Rapamycin Complex 1, Alanine, Muscle Proteins, Parenteral Nutrition, Protein Biosynthesis, mTOR, parenteral nutrition, pig, prematurity, protein synthesis, skeletal muscle

Abstract

BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.

METHODS: Following preterm delivery (on day 105 of 115 gestation), pigs were fitted with umbilical artery and jugular vein catheters and provided continuous parenteral nutrition. Four days after birth, pigs were assigned to receive intermittent Leu (1600 µmol kg

RESULTS: Leu concentration in the longissimus dorsi and gastrocnemius muscles increased in the leucine (LEU) group compared with the alanine (ALA) group (P < 0.0001). Despite the Leu-induced disruption of the Sestrin2·GATOR2 complex, which inhibits mTORC1 activation, in these muscles (P < 0.01), the abundance of mTOR·RagA and mTOR·RagC was not different. Accordingly, mTORC1-dependent activation of 4EBP1, S6K1, eIF4E·eIF4G, and protein synthesis were not different in any muscle between the LEU and ALA groups.

CONCLUSION: Intermittent pulses of Leu do not enhance muscle protein anabolism in preterm pigs supplied continuous parenteral nutrition.