(OR18-04-26) Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Postnatal Linear Growth and Lean Mass Accretion in a Preterm Piglet Model

Objectives: At term-equivalent age, preterm infants are typically shorter and lighter than their term-born peers. Many preterm infants also exhibit suboptimal body composition, characterized by reduced lean mass and elevated adiposity. These early deviations in growth and body composition are linked to an increased long-term risk of obesity and type 2 diabetes, highlighting the need for early-life nutritional strategies that support healthier growth trajectories. We hypothesized that three weeks of pulsatile leucine administration during continuous enteral feeding would enhance linear growth and lean mass accretion in a preterm piglet model.

Methods: Pigs delivered by cesarean section at 105 d of gestation (9 d preterm), equivalent to 30 weeks in human infants, were gradually transitioned over 7 d from parenteral to enteral feeding via an orogastric tube and continuously fed a protein- and energy-balanced milk-replacer diet (195 kcal/kg/d; 13.5 g protein/kg/d). Pigs were randomly assigned to either LEU (1.6 mmol/kg; n = 16) or ALA (1.6 mmol/kg; isonitrogenous control; n = 13). The assigned amino acid solution was administered intravenously as a 1-h pulse every 4 h from d 3 to d 24. Body length and body composition were determined via dual-energy X-ray absorptiometry on d 22, and indices of mTORC1 activation were measured 60 min after the initiation of the last amino acid solution pulse on d 24.

Results: Compared with ALA, LEU pulses increased body length by 4% (P = 0.01) and body weight by 8% (P = 0.02). This growth response was accompanied by a 7% greater total lean mass accretion with LEU (P = 0.05), while body fat percentage remained unchanged. Longissimus dorsi muscle weight and fractional protein synthesis rate were higher in LEU than in ALA (P < 0.05). In the longissimus dorsi, indices of mTORC1‑dependent translation initiation, including phosphorylation of S6K1 and 4EBP1, as well as increased abundance of the eIF4E–eIF4G complex, were also elevated with LEU relative to ALA (P < 0.05).

Conclusions: Pulsatile leucine supplementation during continuous enteral feeding enhanced postnatal linear growth and lean mass accretion without increasing the body fat percentage in preterm pigs. These findings support leucine-based approaches as a potential strategy for promoting healthier body composition following preterm birth.

Funding Sources: NIH and USDA