Interpretive Summary: Nutritional and Endocrine Regulation of Muscle Growth in Neonatal Swine

By: Teresa A. Davis, Agus Suryawan, Ki Beom Jang, and Marta L. Fiorotto (Department of Pediatrics, Baylor College of Medicine, Houston, TX)

Growth is dependent on a higher rate of protein synthesis than degradation and in young animals, is largely attributable to the high rate of protein synthesis.  The ingestion of food stimulates the synthesis of protein in skeletal muscle and this response is profound in early life.  This feeding-induced stimulation of protein synthesis is crucial to support the rapid muscle growth during early postnatal life and the maintenance of body protein in adulthood. Studies in the neonatal pig have shown that the sharp increase in muscle protein synthesis after eating is triggered by the rise in amino acids and insulin.  Amino acids and insulin stimulate protein synthesis by activating independent signaling pathway that converge at mechanistic target of rapamycin complex 1 (mTORC1), leading to the activation of key regulators of mRNA translation, including 4EBP1 and S6K1.  Activation of the insulin receptor by insulin leads to the activation of the signaling pathway that involves Akt, leading to mTORC1 activation. Amino acid signaling involves the interaction of the Rag proteins with mTOR, which results in mTORC1 activation.  The cyclic change in the activation of these signaling proteins with meal feeding parallel the change in protein synthesis.  These responses are high in the neonatal pig born at term and decrease with age.  However, in pigs born prematurely, the protein synthetic response in skeletal muscle to feeding is blunted. This reduced protein synthesis response in the preterm is due to a reduced activation of the insulin and amino acid signaling pathways that lead to mTORC1 and translation initiation factor activation. This anabolic resistance likely contributes to the extrauterine growth restriction and reduced lean growth following premature birth.