Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways

Pediatr Res. 2012 Apr;71(4 Pt 1):324-31. doi: 10.1038/pr.2011.79. Epub 2012 Feb 15.


Introduction: Leucine (Leu) activates mammalian target of rapamycin (mTOR) to upregulate protein synthesis (PS).

Results: PS in skeletal muscles, heart, liver, pancreas, and jejunum, but not kidney, were greater in low protein supplemented with Leu (LP+L) than LP, but lower than high protein (HP). In longissimus dorsi muscle, protein kinase B phosphorylation was similar in LP and LP+L, but lower than HP. Although less than HP, p70 ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E binding protein 1 (4EBP1) association with regulatory associated protein of mammalian target of rapamycin was greater in LP+L than LP, resulting in higher S6K1 and 4EBP1 phosphorylation. Feeding LP+L vs. LP decreased 4EBP1·eIF4E and increased eIF4E·eIF4G formation, but not to HP. Similar results were obtained for S6K1 and 4EBP1 phosphorylation in gastrocnemius, masseter, heart, liver, pancreas, and jejunum, but not kidney. eIF2α and elongation factor 2 phosphorylation was unaffected by treatment. DICUSSION: Our results suggest that enteral Leu supplementation of a low protein diet enhances PS in most tissues through mTOR complex 1 pathways.

Methods: To examine enteral Leu effects on PS and signaling activation, 5-d-old piglets were fed for 24 h diets containing: (i) LP, (ii) LP+L, or (iii) HP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism
  • Dietary Supplements
  • Enteral Nutrition / methods
  • Eukaryotic Initiation Factor-4E / chemistry
  • Eukaryotic Initiation Factor-4G / chemistry
  • Eukaryotic Initiation Factors / chemistry
  • Glycolysis
  • Insulin / blood
  • Leucine / therapeutic use*
  • Muscle, Skeletal / metabolism*
  • Myocardium / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Swine
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors
  • Tissue Distribution


  • Amino Acids
  • Blood Glucose
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factor-4G
  • Eukaryotic Initiation Factors
  • Insulin
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Leucine