Abstract #302

# 302
Long-term leucine and branched-chain amino acid supplementation in a protein and energy deficient diet increases muscle mTORC1 activation in neonatal pigs.
Rodrigo Manjarín*1, Daniel A. Columbus1, Agus Suryawan1, Hanh V. Nguyen1, Adriana Hernández-García1, Rosemarie D. Parada1, Marta L. Forotto1, Teresa Davis1, 1USDA-ARS, Children’s Nutrition Research Center, Houston, TX.

Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants and runt pigs. The objective of this study was to determine if enteral leucine or branched chain amino acid (BCAA) supplementation will upregulate the mammalian target of rapamycin complex 1 (mTORC1) pathway in skeletal muscle and lead to an increase in protein synthesis in neonates who consume only 70% of their protein and energy requirements. Twenty-two 4-d-old piglets were fed by gastric tube 1 of 4 diets, containing (kg body weight−1·d−1) 15 g protein and 215 kcal (CON; n = 5), 10.5 g protein and 156 kcal (R; n = 5), 10.5 g protein + 1.19 g leucine and 156 kcal (RL; n = 6), or 10.5 g protein + 1.67 g BCAA (n = 6) at 4-h intervals for 21 d. On d 21, plasma AA and insulin levels were measured during 6 post-feeding intervals, whereas muscle protein synthesis rate and mTORC1 activation were determined at 120 min post-feeding. Data were analyzed by ANOVA using a linear mixed model with repeated measures. P-values for pre-planned pairwise comparisons were calculated using Student’s t-tests. Compared with CON, the RL and BCAA diets increased plasma leucine levels (P ≤ 0.01), whereas RL decreased isoleucine and valine (P ≤ 0.01) between 0 and 120 min post-feeding. At 120 min insulin was higher in CON compared with R (P ≤ 0.01). Compared with CON, BCAA, RL and R decreased (P < 0.01) body weight gain (3.5, 2.9, 3.0 and 2.9 ± 0.01 kg, respectively), protein synthesis (19.3, 14.2, 15.2 and 14.6 ± 1.3%·d−1), phosphorylation of S6 kinase (p-S6K1; 0.6, 0.4, 0.4 and 0.2 ± 0.01 AU) and 4E-binding protein (p-4EBP1; 0.4, 0.2, 0.2 and 0.1 ± 0.03 AU), and activation of eukaryotic initiation factor 4 complex (eIF4E·eIF4G; 1.5, 1.1, 1.1, and 0.4 ± 0.02 AU). BCAA and RL increased (P ≤ 0.01) p-S6K1, p-4EBP1 and eIF4E·eIF4G compared with R. In conclusion, when protein and energy intakes are restricted, leucine or BCAA supplementation increases muscle mTORC1 activation but does not improve body weight gain or skeletal muscle protein synthesis in neonatal pigs.

Key Words: leucine, neonate, muscle