Preterm birth alters the feeding-induced activation of Akt signaling in muscle of neonatal piglets

BACKGROUND: Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in skeletal muscle of preterm pigs that contributes to lower protein synthesis rates. METHODS: On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined. RESULTS: Akt1 and Akt2, but not Akt3, phosphorylation were lower in skeletal muscle of preterm than term pigs (P < 0.05). Activation of Akt positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term (P < 0.05). PP2A activation was inhibited by feeding in term but not preterm pigs (P < 0.05). CONCLUSION: Our results suggest that preterm birth impairs regulatory components involved in Akt activation, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced lean accretion following preterm birth.