Pulsatile Leucine Administration during Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target of Rapamycin Complex 1 Signaling and Protein Synthesis in a Preterm Piglet Model

Background: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 mu mol Leukg(-1)h(-1) every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle. Objectives: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm. Methods: Pigs delivered 10 d preterm was advanced to full oral feeding >4 d and then assigned to 1 of the following 4 treatments for 28 h: 1) ALA (continuous feeding; pulsed with 800 mu mol alaninekg(-1)h(-1) every 4 h; n = 8); 2) L1x (continuous feeding; pulsed with 800 mu mol Leukg(-1)h(-1) every 4 h; n = 7); 3) L2x (continuous feeding; pulsed with 1600 mu mol Leukg(-1)h(-1) every 4 h; n = 8); and 4) INT (intermittent feeding every 4 h; supplied with 800 mu mol alaninekg(-1) per feeding; n = 7). Muscle protein synthesis rates were determined with L-[H-2(5)-ring]Phenylalanine. The activation of insulin, amino acid, and translation initiation signaling pathways were assessed by Western blot. Results: Peak plasma Leu concentrations were 134% and 420% greater in the L2x compared to the L1x and ALA groups, respectively (P < 0.01). Protein synthesis was greater in the L2x than in the ALA and L1x groups in both the longissimus dorsi and gastrocnemius muscles (P < 0.05) but not different from the INT group (P > 0.10). Amino acid signaling upstream and translation initiation signaling downstream of mTORC1 largely corresponded to the differences in protein synthesis. Conclusions: Intravenous Leu pulses potentiate mTORC1 activity and protein synthesis in the skeletal muscles of continuously fed preterm pigs, but the amount required is greater than in pigs born at term.