Prematurity blunts protein synthesis in skeletal muscle independently of body weight in neonatal pigs

Authors: RUDAR, MARKO - Auburn University; NABERHUIS, JANE - Children'S Nutrition Research Center (CNRC); SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC); NGUYEN, HANH - Children'S Nutrition Research Center (CNRC); FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC); DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2022
Publication Date: 1/10/2023
Citation: Rudar, M., Naberhuis, J.K., Suryawan, A., Nguyen, H.V., Fiorotto, M.L., Davis, T.A. 2023. Prematurity blunts protein synthesis in skeletal muscle independently of body weight in neonatal pigs. Pediatric Research. 94(1):143-152. https://www.nature.com/articles/s41390-022-02456-3.
DOI: https://doi.org/10.1038/s41390-022-02456-3

Interpretive Summary: Approximately 1 in 10 infants in the United States are born preterm. The growth of infants born prematurely is commonly reduced compared to infants born at term. This reduced weight gain is largely due to the reduced growth of their lean tissue, especially skeletal muscle. This reduced growth likely contributes to their increased risk for developing type 2 diabetes, obesity, and cardiovascular disease later in life. We recently demonstrated that the capacity of skeletal muscle to enhance the rate of protein synthesis in response to feeding is reduced in the preterm. However, whether their lower birth weight contributes to their reduced response to feeding has not been determined. To determine whether body weight independently contributes to the blunted responsive to feeding in the preterm, pigs were delivered by Cesarean section, either preterm or at term, and the relationship between birth weight, intracellular nutrient signaling, and protein synthesis in skeletal muscle was evaluated. The average birth weight was lower in the preterm than in the term piglets and the relative birth weight gain was also lower in the preterm than in the term. When the preterm and term pigs were stratified according to birth weight to compare the preterm and term pigs of similar body weight, preterm pigs still exhibited a blunted response to feeding. These findings suggest that preterm birth, and not low birth weight, impairs the capacity of skeletal muscle to stimulate intracellular signaling pathways that regulate protein synthesis. This suggest that a blunted response to feeding contributes to the reduced growth of lean tissue and the altered body composition in preterm infants.

Technical Abstract: Postnatal growth failure in premature infants is associated with reduced lean mass accretion. Prematurity impairs the feeding-induced stimulation of translation initiation and protein synthesis in the skeletal muscle of neonatal pigs. The objective was to determine whether body weight independently contributes to the blunted postprandial protein synthesis. Preterm and term pigs that were either fasted or fed were stratified into quartiles according to birth weight to yield preterm and term groups of similar body weight; first and second quartiles of preterm pigs and third and fourth quartiles of term pigs were compared (preterm-fasted, n = 23; preterm-fed, n = 25; term-fasted, n = 21; term-fed, n = 21). Protein synthesis rates and mechanistic target of rapamycin complex 1 (mTORC1) activation in skeletal muscle were determined. Relative body weight gain was lower in preterm compared to term pigs. Prematurity attenuated the feeding-induced increase in mTORC1 activation in longissimus dorsi and gastrocnemius muscles (P < 0.05). Protein synthesis in gastrocnemius (P < 0.01), but not in longissimus dorsi muscle, was blunted by preterm birth. A lower capacity of skeletal muscle to respond adequately to feeding may contribute to reduced body weight gain and lean mass accretion in preterm infants. This study has shown that the feeding-induced increase in protein synthesis of skeletal and cardiac muscle is blunted in neonatal pigs born preterm compared to pigs born at term independently of birth weight. These findings support the notion that preterm birth, and not low birth weight, impairs the capacity of skeletal and cardiac muscle to upregulate mechanistic target of rapamycin-dependent anabolic signaling pathways and protein synthesis in response to the postprandial increase in insulin and amino acids. These observations suggest that a blunted anabolic response to feeding contributes to reduced lean mass accretion and altered body composition in preterm infants.