scholarly journals Dietary N-carbamylglutamate or L-arginine improves fetal intestinal amino acid profiles during intrauterine growth restriction in undernourished ewes

2021 ◽  
Author(s):  
Hao Zhang ◽  
Xiaoyun Liu ◽  
Yi Zheng ◽  
Ying Zhang ◽  
Juan J. Loor ◽  
...  
Keyword(s):  
Amino Acid ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Amino Acid Profiles

scholarly journals 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

2019 ◽  
Vol 149 (6) ◽  
pp. 923-932 ◽  
Author(s):  
Hao Zhang ◽  
Along Peng ◽  
Yin Yu ◽  
Shuang Guo ◽  
Mengzhi Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Signaling Pathway ◽  
Intrauterine Growth Restriction ◽  
Nutrient Absorption ◽  
Mtor Signaling ◽  
Growth Restriction ◽  
Peptide Transporter ◽  
Mtor Signaling Pathway ◽  
Intrauterine Growth ◽  
Peptide Transporters

ABSTRACT Background 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. Objective 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. Methods 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). Results 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. Conclusion Both NCG and Arg can help mitigate the negative effect of IUGR on nutrient absorption in neonatal lambs.

scholarly journals Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes

animal ◽  
2013 ◽  
Vol 7 (9) ◽  
pp. 1500-1507 ◽  
Author(s):  
C.O. Lemley ◽  
L.E. Camacho ◽  
A.M. Meyer ◽  
M. Kapphahn ◽  
J.S. Caton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Amino Acid Flux

scholarly journals Down-regulation of placental Cdc42 and Rac1 links mTORC2 inhibition to decreased trophoblast amino acid transport in human intrauterine growth restriction

2020 ◽  
Vol 134 (1) ◽  
pp. 53-70 ◽  
Author(s):  
Thomas Jansson ◽  
Marisol Castillo-Castrejon ◽  
Madhulika B. Gupta ◽  
Theresa L. Powell ◽  
Fredrick J. Rosario
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Intrauterine Growth Restriction ◽  
Amino Acid Transporter ◽  
Growth Restriction ◽  
Actin Binding ◽  
Down Regulation ◽  
Intrauterine Growth ◽  
System L ◽  
Acid Transporter

Abstract Intrauterine growth restriction (IUGR) increases the risk for perinatal complications and metabolic and cardiovascular disease later in life. The syncytiotrophoblast (ST) is the transporting epithelium of the human placenta, and decreased expression of amino acid transporter isoforms in the ST plasma membranes is believed to contribute to IUGR. Placental mechanistic target of rapamycin Complex 2 (mTORC2) signaling is inhibited in IUGR and regulates the trafficking of key amino acid transporter (AAT) isoforms to the ST plasma membrane; however, the molecular mechanisms are unknown. Cdc42 and Rac1 are Rho-GTPases that regulate actin-binding proteins, thereby modulating the structure and dynamics of the actin cytoskeleton. We hypothesized that inhibition of mTORC2 decreases AAT expression in the plasma membrane and amino acid uptake in primary human trophoblast (PHT) cells mediated by down-regulation of Cdc42 and Rac1. mTORC2, but not mTORC1, inhibition decreased the Cdc42 and Rac1 expression. Silencing of Cdc42 and Rac1 inhibited the activity of the System L and A transporters and markedly decreased the trafficking of LAT1 (System L isoform) and SNAT2 (System A isoform) to the plasma membrane. mTORC2 inhibition by silencing of rictor failed to decrease AAT following activation of Cdc42/Rac1. Placental Cdc42 and Rac1 protein expression was down-regulated in human IUGR and was positively correlated with placental mTORC2 signaling. In conclusion, mTORC2 regulates AAT trafficking in PHT cells by modulating Cdc42 and Rac1. Placental mTORC2 inhibition in human IUGR may contribute to decreased placental amino acid transfer and reduced fetal growth mediated by down-regulation of Cdc42 and Rac1.

scholarly journals Paternal knockout of Slc38a4/SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice

2019 ◽  
Vol 116 (42) ◽  
pp. 21047-21053 ◽  
Author(s):  
Shogo Matoba ◽  
Shoko Nakamuta ◽  
Kento Miura ◽  
Michiko Hirose ◽  
Hirosuke Shiura ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Embryonic Development ◽  
Intrauterine Growth Restriction ◽  
Molecular Mechanisms ◽  
Growth Restriction ◽  
Metabolome Analysis ◽  
Placental Development ◽  
Short Side ◽  
Intrauterine Growth

The placenta is critical in mammalian embryonic development because the embryo’s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through it. However, the molecular mechanisms underlying this amino acid supply are poorly understood. In this study, we focused on system A amino acid transporters Slc38a1/SNAT1, Slc38a2/SNAT2, and Slc38a4/SNAT4, which carry neutral, short-side-chain amino acids, to determine their involvement in placental or embryonic development. A triple-target CRISPR screen identified Slc38a4/SNAT4 as the critical amino acid transporter for placental development in mice. We established mouse lines from the CRISPR founders with large deletions in Slc38a4 and found that, consistent with the imprinted paternal expression of Slc38a4/SNAT4 in the placenta, paternal knockout (KO) but not maternal KO of Slc38a4/SNAT4 caused placental hypoplasia associated with reduced fetal weight. Immunostaining revealed that SNAT4 was widely expressed in differentiating cytotrophoblasts and maturing trophoblasts at the maternal–fetal interface. A blood metabolome analysis revealed that amino acid concentrations were globally reduced in Slc38a4/SNAT4 mutant embryos. These results indicated that SNAT4-mediated amino acid transport in mice plays a major role in placental and embryonic development. Given that expression of Slc38a4 in the placenta is conserved in other species, our Slc38a4/SNAT4 mutant mice could be a promising model for the analysis of placental defects leading to intrauterine growth restriction in mammals.

Sign in / Sign up

Export Citation Format

Share Document