Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1416-25. doi: 10.1152/ajpendo.00146.2007. Epub 2007 Sep 11.


In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10, whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acids, Branched-Chain / metabolism*
  • Amino Acids, Branched-Chain / pharmacology*
  • Animals
  • Animals, Newborn
  • Endotoxemia / metabolism*
  • Endotoxemia / microbiology
  • Eukaryotic Initiation Factor-4E / metabolism
  • Eukaryotic Initiation Factor-4F / metabolism
  • Female
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Insulin / metabolism
  • Lipopolysaccharides / pharmacology
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Pregnancy
  • Protein Kinases / metabolism
  • Random Allocation
  • Ribosomal Protein S6 Kinases / metabolism
  • Swine
  • Swine Diseases / metabolism*
  • Swine Diseases / microbiology
  • TOR Serine-Threonine Kinases


  • Adaptor Proteins, Signal Transducing
  • Amino Acids, Branched-Chain
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factor-4F
  • Insulin
  • Lipopolysaccharides
  • Muscle Proteins
  • Protein Kinases
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases
  • Glucose