Maturity aggravates sepsis‐associated skeletal muscle catabolism in growing pigs.

Abstract

Synthesis and accretion of muscle protein is elevated in neonates and decreases with development. During sepsis, muscle protein synthesis is reduced, but the effect of development on the metabolic response to sepsis in skeletal muscle is not well understood. 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 (FSR) and translation and degradation signals were determined in longissimus dorsi muscle (n=5–7/group/age). α‐Actin in serum, and FSR, ribosomal abundance, and caspase‐3 abundance in muscle were greater in 7‐ than 26 d‐old pigs, indicating a higher baseline protein turnover in the younger pigs. In muscle, LPS decreased FSR, protein synthetic efficiency, and eIF4G phosphorylation and increased AMPK phosphorylation and MURF‐1 and atrogin‐1 abundance in both age groups. Serum 3‐methylhistidine and α‐actin levels and caspase‐3 abundance in muscle increased in 26‐ but not in 7‐d‐old pigs in response to LPS. The results suggest that the mechanisms regulating protein accretion in skeletal muscle in neonatal pigs during sepsis are influenced by development such that the LPS‐induced muscle catabolism becomes more severe as maturation advances. NIH AR51563, NIH AR44474, and USDA 6250‐51000‐040Grant Funding Source: NIH AR44474, and USDA 6250‐51000‐040