Anabolic signaling and protein deposition are enhanced by intermittent compared with continuous feeding in skeletal muscle of neonates

Abstract

Orogastric tube feeding is indicated for neonates with impaired ability to ingest and can be administered by intermittent bolus or continuous schedule. Our aim was to determine whether feeding modalities affect muscle protein deposition and to identify mechanisms involved. Neonatal pigs were overnight fasted (FAS) or fed the same amount of food continuously (CON) or intermittently (INT; 7 × 4 h meals) for 29 h. For 8 h, between hours 20 and 28, pigs were infused with [(2)H(5)]phenylalanine and [(2)H(2)]tyrosine, and amino acid (AA) net balances were measured across the hindquarters. Insulin, branched-chain AA, phenylalanine, and tyrosine arterial concentrations and whole body phenylalanine and tyrosine fluxes were greater for INT after the meal than for CON or FAS. The activation of signaling proteins leading to initiation of mRNA translation, including eukaryotic initiation factor (eIF)4E·eIF4G complex formation in muscle, was enhanced by INT compared with CON feeding or FAS. Signaling proteins of protein degradation were not affected by feeding modalities except for microtubule-associated protein light chain 3-II, which was highest in the FAS. Across the hindquarters, AA net removal increased for INT but not for CON or FAS, with protein deposition greater for INT. This was because protein synthesis increased following feeding for INT but remained unchanged for CON and FAS, whereas there was no change in protein degradation across any dietary treatment. These results suggest that muscle protein accretion in neonates is enhanced with intermittent bolus to a greater extent than continuous feeding, mainly by increased protein synthesis.

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

“…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.…”

“…Proteins from LD muscle homogenates were subjected to Western blot analysis, as described previously (76 ; Cell Signaling Technology), total Deptor, mTOR, Raptor, Rictor, RagA, RagC, LAM-TOR1, and LAMTOR2 (Cell Signaling Technology), v-ATPase (V0d1 subunit; GeneTex, Irvine, CA), Rheb (R & D Systems, Minneapolis, MN), SLC38A9 (Antibody Verify, Las Vegas, NV), and GAPDH (Abgent, San Diego, CA). Blots were developed as described previously (31). Values for the protein phosphorylation were normalized by their corresponding protein abundance.…”

“…The complex was immunoprecipitated as described previously (31). Amounts of eIF4G were corrected for the amount of eIF4E (Cell Signaling Technology and EMD Millipore) recovered in the immunoprecipitate.…”

“…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.…”

Enteral nutrition for preterm infants: by bolus or continuous? An update

“…10,[11][12][13] Several studies have shown that intermittent bolus feedings reduce the time to achieve full enteral feeds, decrease feeding intolerance and increase weight gain, 14 but contrary results have also been published. 15 Feeding stimulates whole body protein synthesis in the human neonate.…”