Intermittent Bolus Feeding Enhances Organ Growth More Than Continuous Feeding in a Neonatal Piglet Model

Abstract

Background 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. Objective 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. Methods 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 euthanized 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. Results Compared to continuous feeding, intermittent feeding stimulated the growth of the liver (+64%), jejunum (+48%), ileum (+40%), heart (+64%), and kidney (+56%). The increase 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. Conclusions 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.

Intermittent Bolus Compared With Continuous Feeding Enhances Insulin and Amino Acid Signaling to Translation Initiation in Skeletal Muscle of Neonatal Pigs

“…Circulating insulin and amino acid concentrations during the last day of feeding were reported previously (4,23) but are reported here for context. Plasma insulin and amino acid concentrations were constant in the CTS group [insulin = 5.6 ± 0.4 μU/mL; branched-chain amino acid (BCAA) = 1333 ± 94 μmol/L].…”

“…Previously, we reported that intermittent bolus feeding induces higher rates of protein synthesis in skeletal muscle than continuous feeding in a neonatal piglet model (4,23), resulting in an increase in lean growth (4). These results are supported by the findings that intermittent bolus feeding elicits cyclical hormone and substrate patterns in neonatal pigs (24) and preterm human infants (27), and suggest that the insulin and amino acid surges induce greater anabolic activation of the signaling networks that regulate protein synthesis (4,23). However, the molecular mechanisms by which intermittent feeding promotes greater lean growth than continuous feeding have not been fully delineated.…”

“…The research protocol was approved by the Animal Care and Use Committee of the Baylor College of Medicine and was conducted in accordance with the National Research Council's Guide for the Care and Use of Laboratory Animals. The protocol was previously described in El-Kadi et al (4,23) and is briefly described herein. At 2 days of age, female crossbred piglets (Yorkshire x Landrace x Hampshire x Duroc) weighing ∼2 kg (n = 18) underwent surgery to place indwelling catheters into their carotid artery and jugular vein, and a gastrostomy tube for diet delivery as previously described (24).…”

“…In a recent 3-week feeding study in neonatal pigs, we showed that intermittent bolus feeding induces higher rates of mTORC1-dependent protein synthesis in skeletal muscle compared to continuous feeding, resulting in enhanced lean growth (4,23). However, the relative contributions of the insulin-and amino acid-signaling pathways that mediate the effects of these different feeding modalities on protein synthesis and degradation have not been fully elucidated.…”

Intermittent bolus feeding does not enhance protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in a premature piglet model

“…Although continuous feeding may improve feeding tolerance and glycemic stability, the absence of recurring surges in insulin and amino acids may limit muscle protein synthesis and consequently lean growth in the neonate (19)(20)(21)(22). Indeed, prolonged intermittent bolus feeding promotes body weight gain and increases lean mass compared with continuous feeding in neonatal pigs born at term (23,24).…”