Regulation of skeletal muscle protein synthesis in the preterm pig by intermittent leucine pulses during continuous parenteral feeding
Year: 2022
Type: article
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−1 h−1; n = 8) or alanine (1600 µmol kg−1 h−1; n = 8) parenteral pulses every 4 h for 28 h. Anabolic signaling and fractional protein synthesis were determined in skeletal muscle. 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.
DOI: 10.1002/jpen.2450
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Agriculture, Aesculap Akademie, National Institute of Food and Agriculture, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1356634433, G1518131787, G2802688421, G3322068557, Leucine Supplementation to Promote Lean Growth in Early Life, G4172075930, Leucine and HMB Supplementation in Early Life to Promote Muscle Growth at the Expense of Adipose Deposition, G6791272909, G718649217, Regulation of Neonatal Muscle Protein Synthesis, G8023369778, G8117935344, G8400365526, Research Training in Pediatrics Gastroenterolgy, REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS
OpenAlex ID: W4296963695