Developmental changes in the feeding-induced stimulation of translation initiation in muscle of neonatal pigs

The rapid gain in skeletal muscle mass in the neonate is associated with a marked elevation in skeletal muscle protein synthesis in response to feedin g. The feeding-induced response decreases with development. To determine wh ether the response to feeding is regulated at the level of translation init iation, the expression, phosphorylation, and function of a number of eukary otic initiation factors (eIF) were examined. Pigs at 7 and 26 days of age w ere either fasted overnight or fed porcine milk after an overnight fast. In muscle of 7-day-old pigs, the hyperphosphorylated form of the eIF4E repres sor protein, 4E-binding protein 1 (4E-BP1), was undetectable in the fasting state but rose to 60% of total 4E-BP1 after feeding; eIF4E phosphorylation was unaffected by feeding status. The amount of eIF4E in the inactive 4E-B P1.eIF4E complex was reduced by 80%, and the amount of eIF4E in the active eIF4E.eIF4G complex was increased 14-fold in muscle of 7-day-old pigs after feeding. The amount of 70-kDa ribosomal protein S6 (p70(S6)) kinase in the hyperphosphorylated form rose 2.5-fold in muscle of 7-day-old pigs after f eeding. Each of these feeding-induced responses was blunted in muscle of 26 -day-old pigs. eIF2B activity in muscle was unaffected by feeding status bu t decreased with development. Feeding produced similar changes in eIF chara cteristics in liver and muscle; however, the developmental changes in liver were not as apparent as in skeletal muscle. Thus the results demonstrate t hat the developmental change in the acute stimulation of skeletal muscle pr otein synthesis by feeding is regulated by the availability of eIF4E for 48 S ribosomal complex formation. The results further suggest that the overall developmental decline in skeletal muscle protein synthesis involves regula tion by eIF2B.