N-Carbamylglutamate and l-Arginine Promote Intestinal Absorption of Amino Acids by Regulating the mTOR Signaling Pathway and Amino Acid and Peptide Transporters in Suckling Lambs with Intrauterine Growth Restriction

Abstract

Previous studies have revealed that dietary N-carbamylglutamate (NCG) and l-arginine (Arg) improve intestinal integrity, oxidative state, and immune function in Hu suckling lambs with intrauterine growth restriction (IUGR). Whether these treatments alter intestinal nutrient absorption is unknown. The aim of this study was to determine the influence of dietary NCG and Arg treatment during the suckling period on intestinal amino acid (AA) absorption, alterations in the mechanistic target of rapamycin (mTOR) signaling pathway, and the abundance of AA and peptide transporters in IUGR lambs. On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 424 twin lambs. Normal-birth-weight and IUGR Hu lambs were allocated randomly (n=12/group) to a control (4.09±0.12 kg), IUGR (3.52±0.09 kg), IUGR+0.1% NCG (3.49±0.11 kg), or IUGR+1% Arg (3.53±0.10 kg). At day 28, compared with the IUGR group, the IUGR groups receiving NCG and Arg had 7.4% and 7.2% greater (P<0.05) body weight, respectively. Compared with the IUGR group, the serum concentration of insulin was greater (P<0.05) and the cortisol was lower (P<0.05) in the IUGR groups receiving NCG and Arg. Compared with the IUGR group, the IUGR groups receiving NCG and Arg had 13.2%-62.6% greater (P<0.05) serum concentrations of arginine, cysteine, isoleucine, and proline. Dietary NCG or Arg to IUGR lambs resulted in greater protein abundance (P<0.05) of peptide transporter 1 (41.9% or 38.2%) in the ileum compared with the unsupplemented IUGR lambs, respectively. Furthermore, dietary NCG or Arg treatment normalized the IUGR-induced variation (P<0.05) in the ileal ratio of phosphorylated mTOR to total mTOR protein. Both NCG and Arg can help mitigate the negative effect of IUGR on nutrient absorption in neonatal lambs.