Prematurity Attenuates Skeletal Muscle Anabolism of Neonatal Pigs Independently of Birth Weight

OBJECTIVES: Premature infants are at risk for postnatal growth failure that reduces lifelong lean mass. We have shown previously that preterm birth blunts the feeding-induced activation of the mechanistic target of rapamycin (mTOR) signaling pathway, translation initiation, and protein synthesis in skeletal muscle of neonatal pigs. Considering that body weight can vary widely at birth, we sought to separate the effect of prematurity from birth weight on the anabolic response to feeding. METHODS: Pigs were delivered by cesarean section at preterm (103 d) or term (112 d) gestation and fed parenterally for 4 d. On day 4, pigs were fasted for 4 h and were either fasted one additional hour or fed by oral gavage, yielding four groups: 1) preterm fasted (PT-FAST); 2) preterm fed (PT-FED); 3) term fasted (T-FAST); and 4) term fed (T-FED). All pigs were injected with a flooding dose of L-[4-(3)H]Phe to determine fractional protein synthesis rates and euthanized 60 min after feeding or the additional fast. Pigs were stratified by birth weight such that the highest birth weight preterm pigs were compared with the lowest birth weight term pigs (n = 10–13 per group). RESULTS: Despite similar birth weight in preterm and term pigs (1035 vs 993 ± 54 g, P > 0.10), relative weight gain of preterm was 33% lower than term pigs (22.0 vs. 32.9 ± 1.6 g·kg(−1)·d(−1), P < 0.001). Longissimus dorsi (LD), gastrocnemius, and diaphragm protein synthesis rates were not different between PT-FAST and T-FAST groups. Gastrocnemius protein synthesis was 18% lower in PT-FED than T-FED group (P < 0.01), but protein synthesis was not different between PT-FED and T-FED groups in LD and diaphragm muscles. The abundance of the active eIF4E·eIF4G complex and phosphorylation of 4E-BP1 and S6K1, readouts of mTOR activation and translation initiation signaling, were increased after feeding in all muscles (P < 0.001). Translation initiation signaling was lower in LD and gastrocnemius muscles in PT-FED than T-FED groups (P < 0.05) but was not different in diaphragm muscle (P > 0.10). CONCLUSIONS: These findings imply that prematurity, independent of birth weight, blunts mTOR activation and protein synthesis after feeding. The blunted anabolic response to feeding likely underpins postnatal growth failure often observed in infants born preterm. FUNDING SOURCES: NIH and USDA.