Neonatal piglets with intrauterine growth restriction (IUGR) exhibit reduced rates of growth and survival. The present study tested the hypothesis that L-arginine supplementation can mitigate this problem. One hundred and twelve (112) IUGR piglets (with a mean birth weight of 0.84 kg) from 28 sows (four IUGR piglets/sow) were assigned randomly into one of four groups. Piglets were nursed by sows and orally administered 0, 0.1, 0.2, or 0.4 g L-arginine (in the form of L-arginine-HCl) per kg body weight (BW) twice daily between 0 and 14 days of age. The total doses of L-arginine were 0, 0.2, 0.4, or 0.8 g/kg BW/day. Appropriate amounts of L-alanine were added to L-arginine solutions so that all groups of piglets received the same amount of nitrogen. Piglets were weighed on days 0, 7, and 14 of age. On day 14, blood samples (5 mL) were obtained from the jugular vein of piglets at 1 h after suckling, and their milk consumption was measured over a 10-h period using the weigh–suckle–weigh technique. Milk intake did not differ (p > 0.05) among the four groups of piglets. Oral administration of 0.4 g L-arginine/kg BW/day increased (p < 0.05) the circulating levels of arginine, creatine, and anabolic hormones (insulin, growth hormone, and insulin-like growth factor-I), but decreased (p < 0.05) plasma concentrations of ammonia and cortisol (a catabolic hormone). Compared to the control group, IUGR piglets administered 0.2 and 0.4 g L-arginine/kg BW/day increased (p < 0.05) weight gain by 19% and 31%, respectively. Growth did not differ (p > 0.05) between the control and 0.8 g L-arginine/kg BW/day groups. The survival rates of IUGR piglets were 50%, 75%, 89%, and 89%, respectively, for the 0, 0.2, 0.4, and 0.8 g L-arginine/kg BW/day groups. Collectively, these results indicate that the growth and survival of IUGR piglets can be improved through L-arginine supplementation.

Glycine has the greatest rate of deposition in whole-body proteins among all amino acids in neonates, but its provision from sow’s milk meets only 20% of the requirement of suckling piglets. The 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 glycine in the growth of sow-reared IUGR piglets. In Experiment 1, 56 newborn piglets (postnatal day 0) with a low birth weight (<1.10 kg) were selected 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 (BW) twice daily (i.e., 0, 0.2, 0.4 or 0.8 g glycine/kg BW/day) between 0 and 14 days of age. L-Alanine was used as the isonitrogenous control. The BWs 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 muscle protein synthesis in tissues were determined on day 14 using the ³H-phenylalanine flooding dose technique. Compared with piglets in the control group, oral administration of 0.2, 0.4 and 0.8 g glycine/kg BW/day did not affect their milk intake (p > 0.05) but increased (p < 0.05) concentrations of glycine in plasma by 1.52-, 1.94-, and 2.34-fold, respectively, and body weight by 20%, 37%, and 34%, respectively. The dose of 0.4 g glycine/kg BW/day was the most cost-effective. Consistent with its growth-promoting effect, glycine supplementation stimulated (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 (p70^S6K) as well as protein synthesis in skeletal muscle, compared with the control group. Collectively, oral administration of glycine activated the MTOR signaling pathway in skeletal muscle and enhanced the growth performance of IUGR piglets. These results indicate that endogenous synthesis of glycine is inadequate to meet the needs of IUGR piglets during the suckling period and that oral supplementation with glycine to these compromized neonates can improve their growth performance.