Amino acids, independent of insulin, attenuate skeletal muscle autophagy in neonatal pigs during endotoxemia

Pediatr Res. 2016 Sep;80(3):448-51. doi: 10.1038/pr.2016.83. Epub 2016 Apr 11.


Background: Sepsis induces loss of skeletal muscle mass by activating the ubiquitin proteasome (UPS) and autophagy systems. Although muscle protein synthesis in healthy neonatal piglets is responsive to amino acids (AA) stimulation, it is not known if AA can prevent the activation of muscle protein degradation induced by sepsis. We hypothesize that AA attenuate the sepsis-induced activation of UPS and autophagy in neonates.

Methods: Newborn pigs were infused for 8 h with liposaccharide (LPS) (0 and 10 μg·kg(-1)·h(-1)), while circulating glucose and insulin were maintained at fasting levels; circulating AA were clamped at fasting or fed levels. Markers of protein degradation and AA transporters in longissimus dorsi (LD) were examined.

Results: Fasting AA increased muscle microtubule-associated protein light 1 chain 3 II (LC3-II) abundance in LPS compared to control, while fed AA levels decreased LC3-II abundance in both LPS and controls. There was no effect of AA supplementation on activated protein kinase (AMP), forkhead box O1 and O4 phosphorylation, nor on sodium-coupled neutral AA transporter 2 and light chain AA transporter 1, muscle RING-finger protein-1 and muscle Atrophy F-Box/Atrogin-1 abundance.

Conclusion: These findings suggest that supplementation of AA antagonize autophagy signal activation in skeletal muscle of neonates during endotoxemia.

Publication types

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

MeSH terms

  • Amino Acids / blood*
  • Amino Acids, Branched-Chain / blood
  • Animals
  • Animals, Newborn
  • Autophagy / drug effects*
  • Blood Glucose / analysis
  • Blood Urea Nitrogen
  • Endotoxemia / blood
  • Endotoxemia / physiopathology*
  • Insulin / blood*
  • Models, Biological
  • Muscle, Skeletal / pathology*
  • Proteasome Endopeptidase Complex / metabolism
  • Sepsis / physiopathology
  • Sus scrofa
  • Swine
  • Temperature


  • Amino Acids
  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Insulin
  • Proteasome Endopeptidase Complex