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. 2013 Sep 1;305(5):E620-31.
doi: 10.1152/ajpendo.00135.2013. Epub 2013 Jul 9.

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

Claire Boutry  1 , Samer W El-Kadi, Agus Suryawan, Scott M Wheatley, Renán A Orellana, Scot R Kimball, Hanh V Nguyen, Teresa A Davis
Affiliations

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

Claire Boutry et al. Am J Physiol Endocrinol Metab. .

Abstract

Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared with intermittent bolus feeding in neonatal pigs. To determine whether leucine infusion can be used to enhance protein synthesis during continuous feeding, neonatal piglets received the same amount of formula enterally by orogastric tube for 25.25 h continuously (CON) with or without LEU or intermittently by bolus every 4 h (BOL). For the CON+LEU group, leucine pulses were administered parenterally (800 μmol·kg(-1)·h(-1)) every 4 h. Insulin and glucose concentrations increased after the BOL meal and were unchanged in groups fed continuously. LEU infusion during CON feeding increased plasma leucine after the leucine pulse and decreased essential amino acids compared with CON feeding. Protein synthesis in longissimus dorsi (LD), gastrocnemius, and soleus muscles, but not liver or heart, were greater in CON+LEU and BOL than in the CON group. BOL feeding increased protein synthesis in the small intestine. Muscle S6K1 and 4E-BP1 phosphorylation and active eIF4E·eIF4G complex formation were higher in CON+LEU and BOL than in CON but AMPKα, eIF2α, and eEF2 phosphorylation were unchanged. LC3-II-to-total LC3 ratio was lower in CON+LEU and BOL than in CON, but there were no differences in atrogin-1 and MuRF-1 abundance and FoxO3 phosphorylation. In conclusion, administration of leucine pulses during continuous orogastric feeding in neonates increases muscle protein synthesis by stimulating translation initiation and may reduce protein degradation via the autophagy-lysosome, but not the ubiquitin-proteasome pathway.

Keywords: amino acid; infant; orogastric feeding; protein metabolism; translation initiation.

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Figures

Fig. 1.
Fig. 1.
Plasma glucose (A), insulin (B), and glucagon (C) concentrations in piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7). Time is given as hours from initiation of infusion. Statistical effects (interaction of treatment by time, Tt × T) from a mixed model for repeated measures over time are reported for each variable when P < 0.05.
Fig. 2.
Fig. 2.
Plasma essential (A) and nonessential (B) amino acid (AA) concentrations in piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7). Time is given as hours from initiation of infusion. Statistical effects (interaction of Tt × T) from a mixed model for repeated measures over time are reported for each variable when P < 0.05.
Fig. 3.
Fig. 3.
Plasma leucine (A), isoleucine (B), valine (C), and branched-chain AA (D) concentrations in piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7). Time is given as hours from initiation of infusion. Statistical effects (interaction of Tt × T) from a mixed model for repeated measures over time are reported for each variable when P < 0.05.
Fig. 4.
Fig. 4.
Plasma phenylalanine (A), tryptophan (B), histidine (C), lysine (D), methionine (E), and threonine (F) concentrations in piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), and bolus fed (BOL). Values are means ± SE (n = 6–7). Time is given as hours from initiation of infusion. Statistical effects (interaction of Tt × T) from a mixed model for repeated measures over time are reported for each variable when P < 0.05.
Fig. 5.
Fig. 5.
Protein synthesis (KS) in longissimus dorsi (LD; A), gastrocnemius (B), and soleus (C) muscles, heart (D), small intestine (E), and liver (F) in piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7). Statistical effects (Tt) are reported for each variable when P < 0.05 and values with different letters differ significantly (P < 0.05).
Fig. 6.
Fig. 6.
Phosphorylation of S6K1 (A) and 4E-BP1 (B), and eIF4E·eIF4G association (C) in LD muscle of piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7). Statistical effects (Tt) are reported for each variable when P < 0.05 and values with different letters differ significantly (P < 0.05).
Fig. 7.
Fig. 7.
Phosphorylation of AMPKα (A), eIF2α (B), and eEF2 (C) in LD muscle of piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7).
Fig. 8.
Fig. 8.
Phosphorylation of FoxO3 (A), abundance of atrogin-1 (B) and MuRF-1 (C), and the ratio of LC3-II to total LC3 (C) in LD muscle of piglets continuously fed (CON), continuously fed and pulsed with leucine (CON+LEU), or bolus fed (BOL). Values are means ± SE (n = 6–7). Statistical effects (Tt) are reported for each variable when P < 0.05 and values with different letters differ significantly (P < 0.05).
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