Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs.
Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants. The objective of this study was to determine if in neonates who can consume only 70 % of their protein and energy requirements for 8 days, enteral leucine supplementation will upregulate the mammalian target of rapamycin (mTOR) pathway in skeletal muscle, leading to an increase in protein synthesis and muscle anabolism. Nineteen 4-day-old piglets were fed by gastric tube 1 of 3 diets, containing (kg body weight(-1) · day(-1)) 16 g protein and 190 kcal (CON), 10.9 g protein and 132 kcal (R), or 10.8 g protein + 0.2 % leucine and 136 kcal (RL) at 4-h intervals for 8 days. On day 8, plasma AA and insulin levels were measured during 6 post-feeding intervals, and muscle protein synthesis rate and mTOR signaling proteins were determined at 120 min post-feeding. At 120 min, leucine was highest in RL (P < 0.001), whereas insulin, isoleucine and valine were lower in RL and R compared to CON (P < 0.001). Compared to RL and R, the CON diet increased (P < 0.01) body weight, protein synthesis, phosphorylation of S6 kinase (p-S6K1) and 4E-binding protein (p-4EBP1), and activation of eukaryotic initiation factor 4 complex (eIF4E · eIF4G). RL increased (P ≤ 0.01) p-S6K1, p-4EBP1 and eIF4E · eIF4G compared to R. In conclusion, when protein and energy intakes are restricted for 8 days, leucine supplementation increases muscle mTOR activation, but does not improve body weight gain or enhance skeletal muscle protein synthesis in neonatal pigs.
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Rodrigo
R
Manjarín
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Daniel A
DA
Columbus
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Agus
A
Suryawan
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Hanh V
HV
Nguyen
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Adriana D
AD
Hernandez-García
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Nguyet-Minh
NM
Hoang
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Marta L
ML
Fiorotto
U.S. Department of Agriculture/Agricultural Research Service (USDA/ARS), Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Teresa
T
Davis
D000821:Animal Feed / Q000032:analysis*; D000818:Animals; D019587:Dietary Supplements / Q000032:analysis*; D004734:Energy Metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D013552:Swine / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin; D009124:Muscle Proteins; D058570:TOR Serine-Threonine Kinases; D007930:Leucine
Leucine; Muscle; Premature infant; Synthesis