Endotoxin Reduces Muscle Protein Synthesis and Restrains Translation Initiation by Decreasing eIF4G Phosphorylation in Neonatal and Young Pigs

Abstract

Endotoxin (LPS) reduces muscle protein synthesis by restraining translation in the presence of fed levels of insulin and amino acids. In vivo effects of LPS on translation initiation in muscle during basal fasting insulin and amino acid conditions have not been determined in neonates, whose muscle protein synthesis rates are uniquely high. Overnight fasted 7‐ and 26‐d‐old pigs were infused for 8 h with LPS (0 and 10 μg·kg−1·hr−1) and fractional protein synthesis rates and translational control mechanisms in skeletal muscle were examined (n=5–7/group/age). LPS reduced the basal rate of muscle protein synthesis in 7‐ and 26‐day‐old pigs in the presence of fasting levels of insulin, glucose, and amino acids. LPS decreased eIF4G phosphorylation and the amount of the active eIF4G‐eIF4E complex in muscle of 7‐ and 26‐d‐old pigs, but had no effect on mTOR or eEF2 phosphorylation. Although muscle protein synthesis decreased and eEF2 phosphorylation increased with age, there was no effect of age on translation initiation factor activation in basal fasting conditions. The results suggest that the LPS‐induced decrease in eIF4G phosphorylation in muscle may be a limiting step in translation initiation which contributes to the sepsis‐associated decrease in basal protein synthesis rates in muscle during early postnatal life. NIH AR44474, NIH AR51563, NIH HD41648, and USDA 58‐6250‐6‐001.