110 Glycine supplementation activates MTOR cell signaling in skeletal muscle and enhances the growth of sow-reared IUGR pigs.

Abstract Glycine has the greatest rate of deposition in whole-body proteins among all amino acids in neonates, but is remarkably deficient in the milk of mammals including pigs, humans, and cows. Results of our recent studies indicate that piglets with intrauterine growth restriction (IUGR) have a reduced ability to synthesize glycine. The present study determined the role of dietary glycine in the growth of sow-reared IUGR piglets. In Experiment 1, 56 newborn piglets (postnatal day 0) with low birth weights (< 1.10 kg) were from 14 litters, providing 4 IUGR piglets/litter that were allotted randomly into one of four treatment groups (14 piglets/group). Piglets received oral administration of either 0, 0.1, 0.2 or 0.4 g glycine/kg body weight twice daily (i.e., 0, 0.2, 0.4 or 0.8 g glycine/kg body weight/d) between 0 and 14 d of age. L-Alanine was used as the isonitrogenous control. The body weights of all piglets were recorded each week during the experiment. Two weeks after the initiation of glycine supplementation, blood and tissue samples were collected for biochemical analyses. In Experiment 2, rates of protein synthesis in tissues were determined using the 3H-phenylalanine flooding dose technique. Results were analyzed statistically using one-way or two-way ANOVA. The consumption of milk by IUGR piglets measured at 13 d of age was 236 ± 15, 228 ± 12, 244 ± 18, and 240 ± 16 mL/kg BW/d, respectively, in the 0, 0.2, 0.4, and 0.8 g glycine/kg BW/day groups (P > 0.05). Concentrations of serine in plasma were 18% and 25% greater (P < 0.05) in piglets receiving oral administration of 0.4 and 0.8 g glycine/kg BW/day, respectively, than those in the control group. Compared with piglets in the control group, oral administration of 0.2, 0.4 and 0.8 g glycine/kg body weight/d increased (P < 0.05) concentrations of glycine in plasma by 1.52-, 1.94-, and 2.34-fold, respectively, as well as body weight by 20%, 37%, and 34%, respectively. Consistent with its growth-promoting effect, glycine supplementation increased (P < 0.05) the phosphorylation of mechanistic target of rapamycin (MTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and ribosomal protein S6 kinase beta-1 (S6K1) by 330%, 170%, and 180%, respectively, and the fractional rate of protein synthesis by 16%, in longissimus lumborum muscle, compared with the control group. Collectively, oral administration of glycine activated the MTOR signaling pathway in skeletal muscle and promoted the growth performance of IUGR piglets. These results indicate that the endogenous synthesis of glycine is inadequate to meet the metabolic needs of IUGR piglets during the suckling period. (Supported by Agriculture and Food Research Initiative Competitive Grant 2014-67015-21770 from the USDA National Institute of Food and Agriculture)