Regulation of skeletal muscle protein synthetic and degradative signaling by alanyl-glutamine in piglets challenged with Escherichia coli lipopolysaccharide

Nutrition. 2015 May;31(5):749-56. doi: 10.1016/j.nut.2014.11.010. Epub 2014 Dec 19.


Objective: The aim of this study was to investigate the effects of alanyl-glutamine (Ala-Gln) on skeletal muscle protein synthetic and degradative signaling in piglets challenged with Escherichia coli lipopolysaccharide (LPS).

Methods: Piglets were arranged in a 2 × 2 factorial design and the main effects were LPS challenge (0 or 100 units) and diets (0.62% Ala or 0.5% Ala-Gln). After treatment with either Ala or Ala-Gln for 10 d, piglets were injected twice with either saline or LPS on days 11 and 15.

Results: During days 11 to 15 (postchallenge), LPS challenge affected the growth performance of piglets. Ala-Gln supplementation tended to alleviate the reduction of the average daily weight gain (P = 0.071) and the average daily feed intake (P = 0.087) of the LPS-challenged piglets. LPS challenge increased the concentrations of cytokines in plasma (P < 0.05), however, Ala-Gln supplementation prevented the elevation of cortisol induced by LPS challenge (P < 0.05). Moreover, Ala-Gln supplementation increased the mRNA expressions of insulin-like growth factor-1 signaling and Akt (P < 0.05). Ala-Gln supplementation also increased the phosphorylation abundance of the mammalian target of rapamycin, eIF-4 E binding protein 1 and ribosomal protein S6 kinase 1 (P < 0.05). Additionally, Ala-Gln supplementation down-regulated the mRNA abundances of toll-like receptor 4 (TLR4), muscle atrophy F-box, and muscle RING finger 1, which are associated with protein degradation induced by LPS challenge.

Conclusion: Ala-Gln supplementation had beneficial effects in improving protein synthesis signaling of skeletal muscle, and reversed the deleterious changes of signaling molecules in muscle atrophy mainly through down-regulation of Akt/FOXO and TLR4 signaling pathways induced by LPS challenge.

Keywords: Alanyl-glutamine; LPS; Piglet; Signaling pathway; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Supplements
  • Dipeptides / administration & dosage
  • Dipeptides / pharmacology*
  • Eating / drug effects
  • Escherichia coli / chemistry
  • Insulin-Like Growth Factor I / metabolism
  • Lipopolysaccharides / toxicity*
  • Male
  • Muscle Proteins / drug effects*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Peptide Initiation Factors / metabolism
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteolysis / drug effects*
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Signal Transduction / drug effects*
  • Swine
  • Toll-Like Receptor 4 / metabolism
  • Treatment Outcome
  • Weight Gain / drug effects


  • Dipeptides
  • Lipopolysaccharides
  • Muscle Proteins
  • Peptide Initiation Factors
  • Toll-Like Receptor 4
  • eIF-4
  • Insulin-Like Growth Factor I
  • Protein-Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 90-kDa
  • alanylglutamine