NUTRITIONAL REGULATION OF CELL AND ORGAN GROWTH, DIFFERENTIATION, AND DEVELOPMENT
Location: Children Nutrition Research Center (Houston, Tx)
Title: Postnatal ontogeny of skeletal muscle protein synthesis in pigs
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 28, 2007
Publication Date: September 4, 2007
Citation: Davis, T.A., Suryawan, A., Orellana, R.A., Nguyen, H.V., Fiorotto, M.L. 2008. Postnatal ontogeny of skeletal muscle protein synthesis in pigs. Journal of Animal Science. 86(14 Suppl):E13-E18.
Interpretive Summary: The muscles of healthy newborns grow at a very rapid rate. Using baby pigs as our animal model, our research has demonstrated that the rapid growth of muscles in newborns is due to their muscles responding to a meal by rapidly and profoundly increasing the synthesis of muscle proteins. The rise in amino acids and the hormone insulin, which occurs after eating, stimulates the synthesis of proteins in muscle. We have identified many of the intracellular insulin and nutrient signaling proteins that regulate the synthesis of muscle proteins. We have also shown that the activity of these signaling proteins is elevated in muscle of the newborn and that the activity of these signaling proteins decreases with age. These findings are important because by identifying the mechanism that regulates muscle growth in neonate we can learn valuable information so that we can develop better strategies for the nutritional management of low-birth-weight infants.
The neonatal period is characterized by rapid growth and elevated rates of synthesis and accretion of skeletal muscle proteins. The fractional rate of muscle protein synthesis is very high at birth and declines rapidly with age. The elevated capacity for muscle protein synthesis in the neonatal pig is driven by the high ribosome content and, together with an increased efficiency of the translation process, promotes accelerated protein synthesis rates. Feeding profoundly stimulates muscle protein synthesis in neonatal pigs and the response decreases with age. The feeding-induced stimulation of muscle protein synthesis is modulated by an enhanced sensitivity to the postprandial increase in insulin and amino acids. The developmental decline in the response to insulin and amino acids parallels a marked decrease in the feeding-induced activation of translation initiation factors that regulate the binding of mRNA to the 40S ribosomal complex. The abundance and activation of many known positive regulators of the nutrient- and insulin-signaling pathways that are involved in translation initiation are high, whereas those of many negative regulators are low in skeletal muscle of younger pigs. Thus, the activation and(or) abundance of the positive regulators, such as the insulin receptor, insulin receptor-substrate-1, phosphoinositide-3 kinase, phosphoinositide-dependent kinase-1, protein kinase B, mammalian target of rapamycin, raptor, ribosomal protein S6 kinase-1, eukaryotic initiation factor (eIF) 4E-binding protein 1, and eIF4E associated with eIF4G, are greater in 7-d-old pigs than in 26-d-old pigs. The activation of negative regulators, including protein tyrosine phosphatase-1B, phosphatase and tensin homologue deleted on chromosome 10, protein phosphatase 2A, and tuberous sclerosis complex 1/2, are lower in 7-d-old pigs than in 26-d-old pigs. Thus, the developmental decline in the stimulation of skeletal muscle protein synthesis by insulin and amino acids is due in part to the developmentally related decrease in the activation of the signaling pathways that lead to translation initiation.