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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #367935
Title: Prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in muscle of neonatal piglets

Author
item NABERHUIS, JANE - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item SURYAWAN, AGUS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item NGUYEN, HANG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item HERNANDEZ-GARCIA, ADRIANA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item CRUZ, STEPHANIE - MICHAEL DEBAKEY VA MEDICAL CENTER
item LAU, PATRICIO - MICHAEL DEBAKEY VA MEDICAL CENTER
item OLUTOYE, OLUYINKA - MICHAEL DEBAKEY VA MEDICAL CENTER
item STOLL, BARBARA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item Burrin, Douglas - Doug
item FIOROTTO, MARTA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item DAVIS, TERESA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2019
Publication Date: 9/10/2019
Citation: Naberhuis, J.K., Suryawan, A., Nguyen, H.V., Hernandez-Garcia, A., Cruz, S.M., Lau, P.E., Olutoye, O.O., Stoll, B., Burrin, D.G., Fiorotto, M.L., Davis, T.A. 2019. Prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in muscle of neonatal piglets. American Journal of Physiology. https://doi.org/10.1152/ajpendo.00151.2019.
DOI: https://doi.org/10.1152/ajpendo.00151.2019

Interpretive Summary: Worldwide, approximately 15 million infants are born preterm. In newborns, growth is largely driven by the stimulation of protein synthesis in the whole body following a feed. Postnatal growth of lean mass is often blunted in preterm infants and may contribute to short and long-term morbidities. Premature infants demonstrate lower body weight and lean mass than infants born at term, and despite efforts, premature infants leave the hospital weighing less than the 10th percentile for age. To improve outcomes, it is essential to understand the regulatory mechanisms of growth in the perinatal period. Using the neonatal piglet as a model for human infants, we conducted a study to determine whether preterm birth alters the protein anabolic response to feeding. Piglets were delivered at preterm or term and the fractional protein synthesis rates were measured at 3 d of age, while fasted or after an enteral meal. Relative body weight gain was lower in preterm than term. Feeding increased protein synthesis in the longissimus dorsi and gastrocnemius muscles, heart, pancreas, and kidneys, but the response was blunted in the preterm piglets. In the tissues, the activation of the amino acid and insulin signaling proteins that regulate translation initiation were increased by feeding and blunted by prematurity. The results demonstrated that preterm birth reduces weight gain and the protein synthesis response to feeding in muscle, pancreas, and kidney, which is associated with blunted insulin- and/or amino acid-induced translation initiation signaling. These results are important for the bedside care of premature infants.

Technical Abstract: Postnatal growth of lean mass is commonly blunted in preterm infants and may contribute to short- and long-term morbidities. To determine whether preterm birth alters the protein anabolic response to feeding, piglets were delivered at term or preterm and fractional protein synthesis rates (Ks) measured at 3 d of age while fasted or after an enteral elemental meal. Activation of signaling pathways that regulate protein synthesis and degradation were determined. Relative body weight gain was lower in preterm than term pigs. Gestational age at birth (GAB) did not alter fasting plasma glucose or insulin, but when fed, plasma insulin and glucose rose more slowly, and reached peak value later, in preterm than term. Feeding increased Ks in longissimus dorsi (LD) and gastrocnemius muscles, heart, pancreas, and kidney in both GAB groups, but the response was blunted in preterms. In diaphragm, lung, jejunum, and brain, feeding increased Ks regardless of GAB. Liver Ks was greater in preterm than term and increased with feeding regardless of GAB. In all tissues, phosphorylation of 4EBP1, S6K1, and PKB directly mirrored Ks. In LD, eIF4E x eIF4G complex formation, phosphorylation of TSC2, mTOR, and rpS6, and association of mTOR with RagA, RagC, and Rheb were increased by feeding and blunted by prematurity. There were no differences among groups in protein degradation markers in LD. In summary, preterm pigs exhibit decreased weight gain and feeding-induced protein synthesis in muscles, pancreas, and kidney compared to term piglets, which was associated with blunted insulin- and/or amino acid-induced translation initiation signaling.