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Title: Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in 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 WHEATLEY, SCOTT - Children'S Nutrition Research Center (CNRC)
item ORELLANA, RENAN - Children'S Nutrition Research Center (CNRC)
item KIMBALL, SCOT - Pennsylvania State University
item NGUYEN, HANH - 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: 7/3/2013
Publication Date: 7/9/2013
Citation: Boutry, C., El-Kadi, S.W., Suryawan, A., Wheatley, S.M., Orellana, R., Kimball, S.R., Nguyen, H.V., Davis, T.A. 2013. Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs. American Journal of Physiology - Endocrinology and Metabolism. 305:E620-E631.

Interpretive Summary: Babies who are unable to eat normally are fed using feeding tubes. Using baby pigs as a model for human babies, we found that when compared to intermittent meal feeding, continuously tube feeding hinders muscle protein synthesis and, thus, the baby's growth. Since amino acid leucine can stimulate protein synthesis, we conducted a study to determine whether leucine can be beneficial in babies fed with feeding tube. The results of this study show that intermittent infusions of leucine (every 4 hours) to continuous tube feeding induce muscle protein synthesis. Our study suggests that leucine can be used to improve the growth of babies who are receiving feeding tubes, such as in a hospital setting.

Technical 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 leu 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 umol/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 AMPKalpha, eIF2 alpha, 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 autophagylysosome, but not the ubiquitin-proteasome pathway.