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

Claire Boutry, Samer W. El-Kadi, Agus Suryawan, Julia Steinhoff-Wagner, Barbara Stoll, Renán A. Orellana, Hanh V. Nguyen, Scot Kimball, Marta L. Fiorotto, Teresa A. Davis

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11–12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 μmol·kg–1·h–1) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were ~25% greater, and fat gain was 48% lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were ~30% higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates.

Original languageEnglish (US)
Pages (from-to)E699-E713
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume310
Issue number8
DOIs
StatePublished - Apr 15 2016

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Enteral Nutrition
Leucine
Skeletal Muscle
Swine
Polyribosomes
Growth
Phosphorylation
Parenteral Infusions
Proteins
Alanine
Weight Gain
Adenosine Triphosphatases
Therapeutics
Fats
Body Weight
Weights and Measures
Muscles
Messenger RNA
mechanistic target of rapamycin complex 1

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Boutry, Claire ; El-Kadi, Samer W. ; Suryawan, Agus ; Steinhoff-Wagner, Julia ; Stoll, Barbara ; Orellana, Renán A. ; Nguyen, Hanh V. ; Kimball, Scot ; Fiorotto, Marta L. ; Davis, Teresa A. / Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs. In: American Journal of Physiology - Endocrinology and Metabolism. 2016 ; Vol. 310, No. 8. pp. E699-E713.
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abstract = "Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11–12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 μmol·kg–1·h–1) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were ~25{\%} greater, and fat gain was 48{\%} lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were ~30{\%} higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates.",
author = "Claire Boutry and El-Kadi, {Samer W.} and Agus Suryawan and Julia Steinhoff-Wagner and Barbara Stoll and Orellana, {Ren{\'a}n A.} and Nguyen, {Hanh V.} and Scot Kimball and Fiorotto, {Marta L.} and Davis, {Teresa A.}",
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Boutry, C, El-Kadi, SW, Suryawan, A, Steinhoff-Wagner, J, Stoll, B, Orellana, RA, Nguyen, HV, Kimball, S, Fiorotto, ML & Davis, TA 2016, 'Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs', American Journal of Physiology - Endocrinology and Metabolism, vol. 310, no. 8, pp. E699-E713. https://doi.org/10.1152/ajpendo.00479.2015

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs. / Boutry, Claire; El-Kadi, Samer W.; Suryawan, Agus; Steinhoff-Wagner, Julia; Stoll, Barbara; Orellana, Renán A.; Nguyen, Hanh V.; Kimball, Scot; Fiorotto, Marta L.; Davis, Teresa A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 310, No. 8, 15.04.2016, p. E699-E713.

Research output: Contribution to journalArticle

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T1 - Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

AU - Boutry, Claire

AU - El-Kadi, Samer W.

AU - Suryawan, Agus

AU - Steinhoff-Wagner, Julia

AU - Stoll, Barbara

AU - Orellana, Renán A.

AU - Nguyen, Hanh V.

AU - Kimball, Scot

AU - Fiorotto, Marta L.

AU - Davis, Teresa A.

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N2 - Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11–12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 μmol·kg–1·h–1) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were ~25% greater, and fat gain was 48% lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were ~30% higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates.

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