Dietary N-carbamylglutamate or L-arginine supplementation improves hepatic energy status and mitochondrial function and inhibits the AMP-activated protein kinase-peroxisome proliferator-activated receptor γ coactivator-1α-transcription factor A pathway in intrauterine-growth-retarded suckling lambs

Abstract

The objective of this study was to investigate the effects of dietary administration of l -arginine (Arg) or N -carbamylglutamate (NCG) on hepatic energy status and mitochondrial functions in suckling Hu lambs with intrauterine growth retardation (IUGR). Forty-eight newborn Hu lambs of 7 d old were allocated into 4 treatment groups of 12 lambs each, in triplicate with 4 lambs per replicate (2 males and 2 females) as follows: CON (lambs of normal birth weight, 4.25 ± 0.14 kg), IUGR (3.01 ± 0.12 kg), IUGR + 1% Arg (2.99 ± 0.13 kg), or IUGR + 0.1% NCG (3.03 ± 0.11 kg). The experiment lasted for 21 d, until d 28 after birth, and all lambs were fed milk replacer as a basal diet. Compared with IUGR lambs, NCG or Arg administration increased ( P < 0.05) the adenosine triphosphate (ATP) level and the activities of complexes I/III/IV, isocitrate dehydrogenase and citrate synthase in the liver. Compared with CON lambs, the relative mRNA levels of adenosine monophosphate-activated protein kinase α1 ( AMPKα1 ), peroxisome proliferator-activated receptor γ coactivator-1α ( PGC1α ) and transcription factor A ( TFAM ) were increased ( P < 0.05) in the liver of IUGR lambs, but were decreased ( P < 0.05) in the liver of NCG- or Arg-treated lambs compared with those in the IUGR lambs. Compared with IUGR lambs, NCG or Arg administration decreased ( P < 0.05) the total AMPKα (tAMPKα)-to-phosphorylated AMPKα (pAMPKα) ratio and the protein expression of PGC1α and TFAM. The results suggested that dietary Arg or NCG supplements improved hepatic energy status and mitochondrial function and inhibited the AMPK-PGC1α-TFAM pathway in IUGR suckling lambs.

Integration of transcriptomic and metabolomic analysis of the mechanism of dietary N-carbamoylglutamate in promoting follicle development in yaks

“…However, the expression of genes encoding metabolic catalytic enzymes, such as citrate synthase ( CS ), aconitase ( ACO ), malate dehydrogenase ( MDH ), ATP citrate lyase ( ACLY ), and pyruvate carboxylase ( PC ), in the TCA cycle was significantly higher in the NCG group than in the Control group. Previous studies have shown that NCG could improve the activity of the key enzymes associated with the TCA cycle in the intestine and liver of intrauterine growth-restricted fetal lambs ( 71 , 72 ). Besides the pentose phosphate pathway, glucose produces pyruvate via both the aerobic oxidative pathway and the anaerobic glycolytic pathway, and pyruvate is the major energy source for oocytes ( 73 ).…”

The significance of N-carbamoylglutamate in ruminant production

“…Supplementing milk replacer with 0.1% NCG from d 7 to 28 of neonatal life to intra-uterine growth restricted (IUGR) lambs increased their growth rate and improved aspects of hepatic, intestinal and immune function, compared to unsupplemented IUGR lambs [ 62 – 66 , 68 ] but not non-IUGR lambs. In suckling goat kids, NCG supplementation of milk replacer with 100 mg/kg body weight from 1 to 41 days of age increased growth rates and weights of some organs (e.g., spleen) with corresponding increases in the concentration of Arg family AAs in the blood, reduced the incidence of diarrhoea and reduced plasma ammonia and urea N concentrations suggesting a reduction in catabolism of AA, and/or an improvement in the capture of ammonia N in the rumen by microbes [ 66 ]. Wang et al [ 45 ] also reported increased growth rates of kids that were reared by dams supplemented with 2 or 3 g/d of NCG in their basal TMR diet however the mechanisms involved have not been determined.…”

“…Supplementing McCoard and Pacheco Journal of Animal Science and Biotechnology (2023) 14:48 milk replacer with 0.1% NCG from d 7 to 28 of neonatal life to intra-uterine growth restricted (IUGR) lambs increased their growth rate and improved aspects of hepatic, intestinal and immune function, compared to unsupplemented IUGR lambs [62][63][64][65][66]68] but not non-IUGR lambs. In suckling goat kids, NCG supplementation of milk replacer with 100 mg/kg body weight from 1 to 41 days of age increased growth rates and weights of some organs (e.g., spleen) with corresponding increases in the concentration of Arg family AAs in the blood, reduced the incidence of diarrhoea and reduced plasma ammonia and urea N concentrations suggesting a reduction in catabolism of AA, and/or an improvement in the capture of ammonia N in the rumen by microbes [66]. Wang et al [45] also reported increased growth rates of kids that were reared by dams supplemented with 2 or 3 g/d of NCG in their basal TMR diet however the mechanisms involved have not been determined.…”

Dietary N-carbamylglutamate supplementation improves ammonia tolerance of juvenile yellow catfish Pelteobagrus fulvidraco

“…NCG is clinically used to treat urea cycle disorder and restore ureagenesis and normalize blood ammonia levels in patients ( Tuchman et al, 2008 ). In livestock and poultry breeding, NCG can significantly reduce their blood ammonia levels, increase plasma arginine contents, improve growth performance and antioxidant capacity, and inhibit inflammation, such in as chicken Gallus gallus ( Huang et al, 2017 ), pig Susscrofa domestica ( Wu et al, 2010 ; Yang et al, 2011 ), and sheep Ovis aries ( Zhang et al, 2021 ). The vast majority of fish are known to excrete ammonia directly, so their urea cycle pathway may differ from that of mammals and birds ( Anderson, 1995 ).…”