Abstract
Background:
Continuous and intermittent bolus orogastric feedings are strategies used in infants unable to tolerate normal feeds.
Methods:
To determine the effects of feeding modality on protein synthesis in different tissues, neonatal pigs received a balanced formula by orogastric tube as an intermittent bolus feed every 4 h or as a continuous infusion, or were fasted overnight.
Results:
As compared with fasting, protein synthesis in gastrocnemius, masseter, and soleus muscles; left ventricle; liver; pancreas; jejunum; and kidney increased in bolus- and continuously fed pigs, but the greatest increase occurred after a bolus meal. Tuberous sclerosis complex (TSC2), the proline-rich AKT substrate of 40 kDa (PRAS40), eukaryotic initiation factor (eIF) 4E binding protein (4EBP1), and ribosomal protein S6 kinase 1 (S6K1) phosphorylation in all tissues, and the proportion of ribosomal protein S4 in liver polysomes were enhanced 90 min following the bolus meal but not immediately before the meal or during continuous feeding. Eukaryotic elongation factor 2 (eEF2) and eIF2α phosphorylation were unaffected by feeding.
Conclusion:
These results suggest that intermittent bolus feeding increases protein synthesis in muscles of different fiber types and visceral tissues to a greater extent than continuous feeding by stimulating translation initiation.
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References
Ehrenkranz RA . Early, aggressive nutritional management for very low birth weight infants: what is the evidence? Semin Perinatol 2007; 31:48–55.
Saigal S, Stoskopf BL, Streiner DL, Burrows E . Physical growth and current health status of infants who were of extremely low birth weight and controls at adolescence. Pediatrics 2001;108:407–15.
Marchand, V . Enteral nutrition tube feedings. In: Baker S, Baker RD, Davis A, eds. Pediatric Nutrition Support. Sudbury, MA: Jones and Bartlett Publishers, 2007:249–60.
Nutritional needs of the preterm infant. In: Kleinman RE, ed. Pediatric Nutrition Handbook, 5th edn. Elk Grove Village, IL: American Academy of Pediatrics, 2003:23–54.
Aynsley-Green A . The endocrinology of feeding in the newborn. Baillieres Clin Endocrinol Metab 1989;3:837–68.
Mashako MN, Bernard C, Cezard JP, Chayvialle JA, Navarro J . Effect of total parenteral nutrition, constant rate enteral nutrition, and discontinuous oral feeding on plasma cholecystokinin immunoreactivity in children. J Pediatr Gastroenterol Nutr 1987;6:948–52.
Dollberg S, Kuint J, Mazkereth R, Mimouni FB . Feeding tolerance in preterm infants: randomized trial of bolus and continuous feeding. J Am Coll Nutr 2000;19:797–800.
Schanler RJ, Shulman RJ, Lau C, Smith EO, Heitkemper MM . Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method. Pediatrics 1999;103:434–9.
Dsilna A, Christensson K, Alfredsson L, Lagercrantz H, Blennow M . Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants. J Pediatr 2005;147:43–9.
Shulman RJ, Redel CA, Stathos TH . Bolus versus continuous feedings stimulate small-intestinal growth and development in the newborn pig. J Pediatr Gastroenterol Nutr 1994;18:350–4.
Davis TA, Fiorotto ML, Nguyen HV, Reeds PJ . Protein turnover in skeletal muscle of suckling rats. Am J Physiol 1989;257(5 Pt 2):R1141–6.
Denne SC, Rossi EM, Kalhan SC . Leucine kinetics during feeding in normal newborns. Pediatr Res 1991;30:23–7.
Goldspink DF, Kelly FJ . Protein turnover and growth in the whole body, liver and kidney of the rat from the foetus to senility. Biochem J 1984;217:507–16.
Lewis SE, Kelly FJ, Goldspink DF . Pre- and post-natal growth and protein turnover in smooth muscle, heart and slow- and fast-twitch skeletal muscles of the rat. Biochem J 1984;217:517–26.
Davis TA, Fiorotto ML, Beckett PR, et al. Differential effects of insulin on peripheral and visceral tissue protein synthesis in neonatal pigs. Am J Physiol Endocrinol Metab 2001;280:E770–9.
Suryawan A, O’Connor PM, Bush JA, Nguyen HV, Davis TA . Differential regulation of protein synthesis by amino acids and insulin in peripheral and visceral tissues of neonatal pigs. Amino Acids 2009;37:97–104.
O’Connor PM, Kimball SR, Suryawan A, et al. Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs. Am J Physiol Endocrinol Metab 2003;285:E40–53.
O’Connor PM, Kimball SR, Suryawan A, et al. Regulation of neonatal liver protein synthesis by insulin and amino acids in pigs. Am J Physiol Endocrinol Metab 2004;286:E994–E1003.
Ma XM, Blenis J . Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 2009;10:307–18.
Sonenberg N, Hinnebusch AG . Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 2009;136:731–45.
Huang J, Manning BD . A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans 2009;37(Pt 1):217–22.
Wang H, Zhang Q, Wen Q, et al. Proline-rich Akt substrate of 40kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway. Cell Signal 2012;24:17–24.
Wang X, Li W, Williams M, Terada N, Alessi DR, Proud CG . Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J 2001;20:4370–9.
Gazzaneo MC, Suryawan A, Orellana RA, et al. Intermittent bolus feeding has a greater stimulatory effect on protein synthesis in skeletal muscle than continuous feeding in neonatal pigs. J Nutr 2011;141:2152–8.
Premji SS, Chessell L . Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams. Coch Database Syst Rev 2011:CD001819.
Gazzaneo MC, Orellana RA, Suryawan A, et al. Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal. Pediatr Res 2011;70:253–60.
Silvestre MA, Morbach CA, Brans YW, Shankaran S . A prospective randomized trial comparing continuous versus intermittent feeding methods in very low birth weight neonates. J Pediatr 1996;128:748–52.
Bier DM . Intrinsically difficult problems: the kinetics of body proteins and amino acids in man. Diabetes Metab Rev 1989;5:111–32.
Tomé D, Bos C . Dietary protein and nitrogen utilization. J Nutr 2000;130:1868S–73S.
Frank JW, Escobar J, Suryawan A, et al. Protein synthesis and translation initiation factor activation in neonatal pigs fed increasing levels of dietary protein. J Nutr 2005;135:1374–81.
Frank JW, Escobar J, Suryawan A, et al. Dietary protein and lactose increase translation initiation factor activation and tissue protein synthesis in neonatal pigs. Am J Physiol Endocrinol Metab 2006;290:E225–33.
Wilson FA, Suryawan A, Orellana RA, et al. Feeding rapidly stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing translation initiation. J Nutr 2009;139:1873–80.
Suryawan A, Orellana RA, Nguyen HV, Jeyapalan AS, Fleming JR, Davis TA . Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated. Am J Physiol Endocrinol Metab 2007;293:E1597–605.
Davis TA, Fiorotto ML . Regulation of muscle growth in neonates. Curr Opin Clin Nutr Metab Care 2009;12:78–85.
Suryawan A, Davis TA . The abundance and activation of mTORC1 regulators in skeletal muscle of neonatal pigs are modulated by insulin, amino acids, and age. J Appl Physiol 2010;109:1448–54.
Martineau Y, Derry MC, Wang X, et al. Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation. Mol Cell Biol 2008;28:6658–67.
Jefferies HB, Fumagalli S, Dennis PB, Reinhard C, Pearson RB, Thomas G . Rapamycin suppresses 5’TOP mRNA translation through inhibition of p70s6k. EMBO J 1997;16:3693–704.
Sherton CC, Wool IG . Determination of the number of proteins in liver ribosomes and ribosomal subunits by two-dimensional polyacrylamide gel electrophoresis. J Biol Chem 1972;247:4460–7.
Wool IG, Chan YL, Paz V, Olvera J . The primary structure of rat ribosomal proteins: the amino acid sequences of L27a and L28 and corrections in the sequences of S4 and S12. Biochim Biophys Acta 1990;1050:69–73.
Kimball SR, Jefferson LS . Control of protein synthesis by amino acid availability. Curr Opin Clin Nutr Metab Care 2002;5:63–7.
Kimball SR, Jefferson LS . Regulation of global and specific mRNA translation by oral administration of branched-chain amino acids. Biochem Biophys Res Commun 2004;313:423–7.
Anthony JC, Anthony TG, Kimball SR, Jefferson LS . Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 2001;131:856S–60S.
Davis TA, Burrin DG, Fiorotto ML, Nguyen HV . Protein synthesis in skeletal muscle and jejunum is more responsive to feeding in 7-than in 26-day-old pigs. Am J Physiol 1996;270(5 Pt 1):E802–9.
Acknowledgements
We thank Robert Shulman and Douglas Burrin for helpful discussions, Rosemarie Almonaci and Sue Koo for technical assistance, Jerome Stubblefield for animal care, and E. O’Brian Smith for statistical assistance.
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El-Kadi, S., Gazzaneo, M., Suryawan, A. et al. Viscera and muscle protein synthesis in neonatal pigs is increased more by intermittent bolus than by continuous feeding. Pediatr Res 74, 154–162 (2013). https://doi.org/10.1038/pr.2013.89
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DOI: https://doi.org/10.1038/pr.2013.89
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