Intermittent Bolus Feeding Has a Greater Stimulatory Effect on Protein Synthesis in Skeletal Muscle Than Continuous Feeding in Neonatal Pigs

Abstract

Orogastric tube feeding, using either continuous or intermittent bolus delivery, is common in infants for whom normal feeding is contraindicated. To compare the impact of different feeding strategies on muscle protein synthesis, after withholding food overnight, neonatal pigs received a complete formula orally as a bolus feed every 4 h or were continuously fed. Protein synthesis rate and translational mechanisms in skeletal muscle were examined after 0, 24, and 25.5 h. Plasma amino acid and insulin concentrations increased minimally and remained constant in continuously fed compared to feed-deprived pigs; however, the pulsatile meal feeding pattern was mimicked in bolus-fed pigs. Muscle protein synthesis was stimulated by feeding and the greatest response occurred after a bolus meal. Bolus but not continuous feeds increased polysome aggregation, the phosphorylation of protein kinase B, tuberous sclerosis complex 2, proline-rich Akt substrate of 40 kDa, eukaryotic initiation factor (eIF) 4E binding protein (4EBP1), and rp S6 kinase and enhanced dissociation of the 4EBP1 ·eIF4E complex and formation of the eIF4E ·eIF4G complex compared to feed deprivation (P < 0.05). Activation of insulin receptor substrate-1, regulatory associated protein of mammalian target of rapamycin, AMP-activated protein kinase, eukaryotic elongation factor 2, and eIF2α phosphorylation were unaffected by either feeding modality. These results suggest that in neonates, intermittent bolus feeding enhances muscle protein synthesis to a greater extent than continuous feeding by eliciting a pulsatile pattern of amino acid- and insulin-induced translation initiation.

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

“…This is consistent with the lack of effect of leucine pulses on the abundance of ribosomal protein S4 and S8 mRNA in polysomes, suggesting that leucine pulses may not stimulate ribosomal biogenesis. Although intermittent bolus feeding increases the aggregation of ribosomes on mRNA in skeletal muscle more than continuous feeding (40), in this study we could not detect an effect of leucine pulses on the proportion of ribosomes in polysomes. …”

“…Recent findings in our neonatal piglet model have demonstrated that continuous feeding by orogastric tube reduces protein synthesis and blunts protein deposition compared with intermittent bolus feeding for 24 h (31,32,40). This reduced response to the same nutrient load is due to the relatively suppressed and constant hormone and substrate patterns incurred with continuous feeding that attenuate muscle protein synthesis.…”

“…mammalian) target of rapamycin (mTOR), which regulates translation initiation (21,62,76). We have shown that intermittent bolus feeding enhances muscle protein synthesis by inducing a pulsatile pattern of amino acid-and insulin-stimulated translation initiation (20,40). However, the low and constant hormone and substrate patterns elicited by continuous feeding attenuate translation initiation signaling.…”

“…neonatal pig as a model for the human neonate, that continuous feeding blunts protein synthesis and reduces protein deposition compared with intermittent bolus feeding, even though the same nutrient load is consumed (20,31,40). Thus, strategies are needed to improve the growth of neonates who require continuous feeding.…”

Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs

“…Although intermittent bolus feeding has been advocated because it is more physiological, as it mimics the hormonal profile of meal feeding, continuous feeding is still indicated for some patients due to feeding intolerance (20,58). Recently, we demonstrated, using neonatal pigs as a model for the human neonate, that orogastric continuous feeding blunts protein synthesis in skeletal muscle compared with intermittent bolus feeding (26,32).…”