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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #331025

Research Project: Molecular, Cellular, and Regulatory Aspects of Nutrition During Development

Location: Children's Nutrition Research Center

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

Author
item Boutry, Claire - Children'S Nutrition Research Center (CNRC)
item El-kadi, Samer - Children'S Nutrition Research Center (CNRC)
item Suryawan, Agus - Children'S Nutrition Research Center (CNRC)
item Steinhoff-wagner, Julia - Children'S Nutrition Research Center (CNRC)
item Stoll, Barbara - Children'S Nutrition Research Center (CNRC)
item Orellana, Renan - Children'S Nutrition Research Center (CNRC)
item Nguyen, Hanh - Children'S Nutrition Research Center (CNRC)
item Kimball, Scot - Children'S Nutrition Research Center (CNRC)
item Fiorotto, Marta - Children'S Nutrition Research Center (CNRC)
item Davis, Teresa - Children'S Nutrition Research Center (CNRC)

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2016
Publication Date: 4/15/2016
Citation: Boutry, C., El-Kadi, S.W., Suryawan, A., Steinhoff-Wagner, J., Stoll, B., Orellana, R.A., Nguyen, H.V., Kimball, S.R., Fiorotto, M.L., Davis, T.A. 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. 310(8):699-713.

Interpretive Summary: Many low-birth-weight infants are fed formula or human milk by gastric tube either continuously at a constant flow rate or intermittently to mimic meal feeding. Researchers at the Children's Nutrition Research Center in Houston, Texas previously showed using a neonatal piglet model that the synthesis of proteins in muscle is reduced in newborns that were continuously fed compared to intermittently fed. However, because some low-birth-weight infants must be fed continuously due to feeding intolerance, alternative nutritional strategies are needed to improve their lean growth. We found that when neonatal piglets are continuously fed an optimal diet, further supplementation with intermittent pulses of the amino acid, leucine, enhances lean growth by stimulating the synthesis of muscle protein. These results suggest that leucine supplementation may be a useful nutritional therapy to improve lean growth in low-birth-weight infants.

Technical 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 previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared to 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 d with an additional parenteral infusion of either leucine (800 umol/kg-1/h-1, CON+LEU) 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 to CON+ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4EBP1 and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2a, 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 d of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway leading to protein synthesis in skeletal muscle of neonates.