351. Leucine Supplementation Enhances Postnatal Growth and Lean Mass Without Increasing Adiposity in a Preterm Piglet Model.

Abstract Postnatal growth is commonly impaired in low-birth-weight infants and piglets and contributes to increased morbidity and mortality rates. Premature birth is a major contributor to low birth weight in infants and is associated with postnatal growth faltering, which is largely attributed to reduced lean mass accretion accompanied by increased adiposity. This altered early body composition in infants is associated with an increased long-term risk of obesity and type 2 diabetes. Optimizing nutritional strategies to enhance lean tissue growth may therefore mitigate postnatal growth faltering and adverse chronic health outcomes. Using preterm piglets, a highly relevant translational model for the premature human infant, we hypothesized that intermittent pulses of leucine provided during continuous enteral feeding would enhance postnatal growth, stimulate skeletal muscle protein synthesis, and promote lean mass accretion. Piglets were delivered by cesarean section at 105 days of gestation (9 days preterm; equivalent to ∼30 weeks of human gestation) and transitioned over 7 days from parenteral to enteral nutrition delivered via an orogastric tube. Animals were continuously fed a protein- and energy-balanced milk replacer (195 kcal/kg/day; 13.5 g protein/kg/day) and randomly assigned to receive either leucine (LEU; 1.6 mmol/kg; n = 16) or an isonitrogenous alanine control (ALA; 1.6 mmol/kg; n = 13). Assigned amino acids were administered intravenously as a 1-hour pulse every 4 hours from day 3 to day 24. Body composition was measured by dual-energy X-ray absorptiometry on day 22. Fractional protein synthesis rates and signaling components were determined postprandially, 60 minutes after initiation of the final amino acid pulse on day 24. Average daily gain, final body weight, body length, and longissimus dorsi muscle weight relative to body weight were greater in LEU compared with ALA pigs (P < 0.05). Total lean mass accretion was increased by 7% in LEU pigs (P = 0.05), whereas body fat percentage did not differ between groups. Fractional protein synthesis rates in the longissimus dorsi and gastrocnemius muscles were greater with LEU supplementation (P < 0.05). Upstream regulators of mTORC1 signaling indicated reduced abundance of the inhibitory Sestrin2–GATOR2 complex and increased abundance of the RagA–mTORC1 complex in LEU pig skeletal muscles (P < 0.05). Downstream of mTORC1, phosphorylation of S6K1 and 4EBP1 and abundance of the eIF4E–eIF4G complex were greater in the skeletal muscles of LEU compared with ALA pigs (P < 0.05). Indices of protein degradation (MuRF1, Atrogin-1, and LC3) did not differ between groups. In conclusion, pulsatile leucine supplementation during continuous enteral feeding enhances postnatal growth and lean mass accretion without increasing adiposity in preterm pigs. These findings support leucine-based strategies as a potential nutritional approach to promote healthier body composition following preterm birth.