Location: Children's Nutrition Research CenterTitle: Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal Author
Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2011
Publication Date: 9/1/2011
Citation: Gazzaneo, M.C., Orellana, R.A., Suryawan, A., Tuckow, A.P., Kimball, S.R., Wilson, F.A., Nguyen, H.V., Torrazza, R.M., Fiorotto, M.L., Davis, T.A. 2011. Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal. Pediatric Research. 70(3):253-260. Interpretive Summary: Healthy newborns grow very rapidly. Our research has shown that this rapid rate of growth in the newborn occurs because the rate at which their tissues synthesize protein increases profoundly when they eat. However, the mechanism by which this occurs has not been clearly understood. Using the baby pig as an animal model, we showed that the rise in the blood of the hormone insulin, as well as amino acids, which are the building blocks of protein, after a meal stimulates the intracellular signaling pathway that regulates protein synthesis. This stimulation of protein synthesis is rapid but is more sustained in skeletal muscles that are of fast-twitch white fiber type than in those of slow-twitch red fiber type. The response also varies among visceral tissues. The greatest and most persistent stimulation of protein synthesis occurs in liver, whereas the response is blunted in the kidney. These findings provide insights into the process involved in the stimulation of protein synthesis in different tissues after a meal and will help us find optimal ways of supporting the growth and development of babies.
Technical Abstract: Protein synthesis (PS) increases after a meal in neonates, but the time course of the changes in PS in different tissues after a meal is unknown. We aimed to evaluate the changes in tissue PS, mammalian target of rapamycin complex 1 (mTORC1) activation, and proportion of ribosomal protein (rp) mRNAs in polysomes over 4 h after a bolus meal in neonatal pigs (6/group; 5- to 7-d-old). The results show a more sustained increase in PS in glycolytic compared with mixed fiber type muscles and no changes in oxidative muscles. PS increased in liver, jejunum, and pancreas but not in kidney and heart. Feeding did not affect AMP-activated protein kinase or RAS-related GTP binding B activation. Phosphorylation of tuberous sclerosis complex 2, prolinerich Akt substrate of 40 kD, mTOR, eukaryotic initiation factor 4E binding protein, and rp S6 kinase 1 increased in all tissues after feeding. The proportion of mRNAs encoding rp S4 and S8 in liver polysomes increased within 30 min postfeeding. These results suggest that feeding stimulates mTORC1 signaling in muscle and viscera, but mTORC1 activation alone is not sufficient to stimulate PS in all tissues.