Intermittent bolus feeding enhances organ growth more than continuous feeding in a neonatal piglet model

Authors: EL-KADI, SAMER - Children'S Nutrition Research Center (CNRC); BOUTRY-REGARD, CLAIRE - Children'S Nutrition Research Center (CNRC); SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC); NGUYEN, HANH - Children'S Nutrition Research Center (CNRC); KIMBALL, SCOT - Children'S Nutrition Research Center (CNRC); FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC); DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Current Developments in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/13/2020
Publication Date: 11/24/2020
Citation: El-Kadi, S.W., Boutry-Regard, C., Suryawan, A., Nguyen, H.V., Kimball, S.R., Fiorotto, M.L., Davis, T.A. 2020. Intermittent bolus feeding enhances organ growth more than continuous feeding in a neonatal piglet model. Current Developments in Nutrition. 4(12):nzaa170. https://doi.org/10.1093/cdn/nzaa170.
DOI: https://doi.org/10.1093/cdn/nzaa170

Interpretive Summary: When infants cannot ingest food properly, orogastric tube feeding is provided either as intermittent bolus meals or continuously. Intermittent bolus feeding is often preferred, but some infants cannot tolerate normal meal feeding and must be fed continuously. Using the neonatal piglet as a model for human infants, we previously demonstrated that intermittent bolus feeding promotes greater growth of skeletal muscle by upregulating intracellular translation initiation signaling that regulates protein synthesis. To determine the long-term effects of feeding modality on organ growth and the mechanisms involved, we used neonatal pigs fed either intermittently or continuously for 21 days. We showed that intermittent bolus feeding, compared to continuous feeding, enhanced the growth of the liver, jejunum, ileum, heart, and kidneys. These increases in the mass of most organs were proportional to the gain in whole-body lean weight but was even greater in the liver. Intermittent bolus feeding also increased the fractional rate of protein synthesis in the liver and ileum and this was associated with an increase in the activation of translation initiation factors that regulate protein synthesis. The results of our study demonstrate that, compared to continuous bolus feeding, intermittent bolus feeding enhances organ growth by stimulating the translation initiation signaling pathway that regulates protein synthesis.

Technical Abstract: Orogastric tube feeding is frequently prescribed for neonates who cannot ingest food normally. In a piglet model of the neonate, greater skeletal muscle growth is sustained by upregulation of translation initiation signaling when nutrition is delivered by intermittent bolus meals, rather than continuously. The objective of this study was to determine the long-term effects of feeding frequency on organ growth and the mechanism by which feeding frequency modulates protein anabolism in these organs. Eighteen neonatal pigs were fed by gastrostomy tube the same amount of a sow milk replacer either by continuous infusion (CON) or on an intermittent bolus schedule (INT). After 21 d of feeding, the pigs were killed without interruption of feeding (CON; n = 6) or immediately before (INT-0; n = 6) or 60 min after (INT-60; n = 6) a meal, and fractional protein synthesis rates and activation indexes of signaling pathways that regulate translation initiation were measured in the heart, jejunum, ileum, kidneys, and liver. Compared with continuous feeding, intermittent feeding stimulated the growth of the liver (+64%), jejunum (+48%), ileum (+40%), heart (+64%), and kidney (+56%). The increases in heart, kidney, jejunum, and ileum masses were proportional to whole body lean weight gain, but liver weight gain was greater in the INT-60 than the CON, and intermediate for the INT-0 group. For the liver and ileum, but not the heart, kidney, and jejunum, INT-60 compared with CON pigs had greater fractional protein synthesis rates (22% and 48%, respectively) and was accompanied by an increase in ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E binding protein 1 phosphorylation. These results suggest that intermittent bolus compared with continuous orogastric feeding enhances organ growth and that in the ileum and liver, intermittent feeding enhances protein synthesis by stimulating translation initiation.