AMINO ACIDS STIMULATE MUSCLE PROTEIN SYNTHESIS IN NEONATES DURING ENDOTOXEMIA DESPITE REPRESSION OF TRANSLATION INITIATION

Abstract

In adults, sepsis reduces protein synthesis in skeletal muscle by restraining translation initiation. In contrast, neonates are highly anabolic and their muscle protein synthesis rates are elevated and very sensitive to amino acid stimulation. We studied the effect of sepsis on amino acid-stimulated muscle protein synthesis in fasted neonatal pigs by infusing endotoxin (LPS, 0 and 10 μg?kg−1?hr−1) for 8 h. Glucose and insulin were maintained at fasting levels, amino acids (AA) were clamped either at fasting or fed levels, fractional protein synthesis rates were determined, and translational control mechanisms were examined. In the presence of fasting AA levels, LPS reduced protein synthesis in longissimus dorsi (LD) muscle (−20%), increased the inactive eIF4E/4E-BP1 binding, and decreased S6K1 phosphorylation. Raising AA to fed levels accelerated muscle protein synthesis rates (controls: +80%; LPS: +57%), increased 4E-BP1 and S6K1 phosphorylation, and tended to decrease the phosphorylation of eEF2 in muscle of control but not LPS animals. These findings suggest that muscle protein synthesis in neonatal pigs is reduced by endotoxemia during fasting, but the response of muscle protein synthesis to amino acid stimulation is maintained, despite suppression of translation initiation. NIH AR44474, NIH AR51563, NIH HD41648, and USDA 58-6250-6-001.