PSVII-7 - Prematurity Alters the Regulation of Akt Signaling in Skeletal Muscle of Piglets

Objectives: Postnatal growth faltering is common after preterm birth. Recently we showed that premature birth in piglets impairs normal postnatal weight gain and skeletal muscle protein synthesis compared to piglets born at term. This response is associated with a reduction in the feeding-induced activation of Akt and subsequent downstream signaling, despite no change in insulin receptor activation. The aim of this study was to identify key regulators of Akt responsible for the blunted anabolic response in preterm muscle.

Methods: Piglets delivered by cesarean section 11 d (preterm/PT) or 2 d (term/T) before term birth were fed by total parenteral nutrition. On day 3, after 4 h fasting, piglets were fasted one additional h or fed orally a sow milk replacer (per kg body weight: 31.5 kcal, 1.3 g carbohydrate, 2.7 g amino acids BW, 1.6 g lipid ). Positive and negative regulators of Akt activity in longissimus dorsi muscle were determined by Western blot.

Results: Phosphorylation of Akt1 and Akt2, but not Akt3, was lower in PT than in T pigs (P < 0.05). Phosphorylation of Akt activators, PDK1 and mTORC2, and the abundance of Ubl4A, a positive regulator of Akt, were lower in PT than in T (P < 0.05). Abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN, was higher in PT than in T (P < 0.05). Activation of the Akt phosphatase, PP2A, was unaffected by feeding in PT but inhibited by feeding in T pigs (P < 0.05).

Conclusions: These results show that the feeding-induced activation of positive regulators of Akt is reduced by preterm birth, whereas the activation of negative regulators is enhanced. Our findings suggest that premature birth impairs the activation of Akt that is essential for channeling dietary nutrients for anabolism and likely contributes to the postnatal growth faltering of prematurity. Research Support: NIH and USDA.