Development aggravates the severity of skeletal muscle catabolism induced by endotoxemia in neonatal pigs

Am J Physiol Regul Integr Comp Physiol. 2012 Mar 15;302(6):R682-90. doi: 10.1152/ajpregu.00259.2011. Epub 2012 Jan 25.


Accretion rates of muscle protein are elevated in normal neonates, but this anabolic drive decreases with maturation. As this change occurs, it is not known whether development also influences muscle protein catabolism induced by sepsis. We hypothesize that protein degradation in skeletal muscle induced by endotoxemia becomes more severe as the neonate develops. Fasted 7- and 26-day-old pigs were infused for 8 h with LPS (0 and 10 μg·kg(-1)·h(-1)), while plasma amino acids (AA), 3-methylhistidine (3-MH), and α-actin concentrations and muscle protein degradation signal activation were determined (n = 5-7/group/age). Plasma full-length α-actin was greater in 7- than 26-day-old pigs, suggesting a higher baseline protein turnover in neonatal pigs. LPS increased plasma total AA, 3-MH, and full-length and cleaved α-actin in 26- than in 7-day-old pigs. In muscle of both age groups, LPS increased AMPK and NF-κB phosphorylation, the abundances of activated caspase 3 and E-3 ligases MuRF1 and atrogin1, as well as the abundance of cleaved α-actin, suggesting activation of muscle proteolysis by endotoxin in muscle. LPS decreased Forkhead box 01 (Fox01) and Fox04 phosphorylation and increased procaspase 3 abundance in muscle of 26-day-old pigs despite the lack of effect of LPS on PKB phosphorylation. The results suggest that skeletal muscle in healthy neonatal pigs maintains high baseline degradation signal activation that cannot be enhanced by endotoxin, but as maturation advances, the effect of LPS on muscle protein catabolism manifests its severity.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Actins / blood
  • Amino Acids / blood
  • Animals
  • Animals, Newborn / metabolism*
  • Animals, Newborn / microbiology
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Endotoxemia / metabolism*
  • Endotoxemia / physiopathology
  • Endotoxins / pharmacology
  • Escherichia coli Infections / metabolism*
  • Escherichia coli Infections / physiopathology
  • Insulin / blood
  • Metabolism / drug effects
  • Metabolism / physiology*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiopathology
  • NF-kappa B / metabolism
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Severity of Illness Index*
  • Swine / growth & development*
  • Swine / metabolism


  • Actins
  • Amino Acids
  • Endotoxins
  • Insulin
  • Muscle Proteins
  • NF-kappa B
  • endotoxin, Escherichia coli
  • Protein Kinases
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinase Kinases
  • Caspase 3