scholarly journals The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Xin Wu ◽  
Yongmin Zheng ◽  
Jie Ma ◽  
Jie Yin ◽  
Shuai Chen

Inflammatory bowel disease, a gut disease that is prevalent worldwide, is characterized by chronic intestinal inflammation, such as colitis, and disorder of the gut microbiome. Glycine (Gly) is the simplest amino acid and functions as an anti-inflammatory immune-nutrient and intestinal microbiota regulator. This study aimed at investigating the effect of Gly on colitis induced in mice by intrarectal administration of 5% acetic acid (AA). Bodyweight and survival rates were monitored, and colonic length and weight, serum amino acid concentrations, intestinal inflammation-related gene expression, and colonic microbiota abundances were analyzed. The results showed that Gly dietary supplementation had no effect on the survival rate or the ratio of colonic length to weight. However, Gly supplementation reversed the AA-induced increase in serum concentrations of amino acids such as glutamate, leucine, isoleucine, and valine. Furthermore, Gly inhibited colonic gene expression of interleukin- (IL-) 1β and promoted IL-10 expression in colitis mice. Gly supplementation also reversed the AA-induced reduction in the abundance of bacteria such as Clostridia, Ruminococcaceae, and Clostridiales. This change in the intestinal microbiota was possibly attributable to the changes in colonic IL-10 expression and serum concentrations of valine and leucine. In sum, Gly supplementation regulated the serum concentrations of amino acids, the levels of colonic immune-associated gene expression, and the intestinal microbiota in a mouse model of colitis. These findings enhance our understanding of the role of Gly in regulating metabolism, intestinal immunity, and the gut microbiota in animals afflicted with colitis.

2022 ◽  
Vol 8 ◽  
Author(s):  
Qing Duanmu ◽  
Bie Tan ◽  
Jing Wang ◽  
Bo Huang ◽  
Jianjun Li ◽  
...  

Dietary supplementation with aromatic amino acids (AAAs) has been demonstrated to alleviate intestinal inflammation induced by lipopolysaccharide (LPS) in the piglets. But the mechanism of AAA sensing and utilization under inflammatory conditions is not well-understood. The study was conducted with 32 weanling piglets using a 2 × 2 factorial arrangement (diet and LPS challenge) in a randomized complete block design. Piglets were fed as basal diet or the basal diet supplemented with 0.16% tryptophan (Trp), 0.41% phenylalanine (Phe), and 0.22% tyrosine (Tyr) for 21 days. The results showed that LPS treatment significantly reduced the concentrations of cholecystokinin (CCK) and total protein but increased leptin concentration, the activities of alanine transaminase, and aspartate aminotransferase in serum. Dietary supplementation with AAAs significantly increased the serum concentrations of CCK, peptide YY (PYY), and total protein but decreased the blood urea nitrogen. LPS challenge reduced the ileal threonine (Thr) digestibility, as well as serum isoleucine (Ile) and Trp concentrations, but increased the serum concentrations of Phe, Thr, histidine (His), alanine (Ala), cysteine (Cys), and serine (Ser) (P < 0.05). The serum-free amino acid concentrations of His, lysine (Lys), arginine (Arg), Trp, Tyr, Cys, and the digestibilities of His, Lys, Arg, and Cys were significantly increased by feeding AAA diets (P < 0.05). Dietary AAA supplementation significantly increased the serum concentrations of Trp in LPS-challenged piglets (P < 0.05). In the jejunal mucosa, LPS increased the contents of Ala and Cys, and the mRNA expressions of solute carrier (SLC) transporters (i.e., SLC7A11, SLC16A10, SLC38A2, and SLC3A2), but decreased Lys and glutamine (Gln) contents, and SLC1A1 mRNA expression (P < 0.05). In the ileal mucosa, LPS challenge induced increasing in SLC7A11 and SLC38A2 and decreasing in SLC38A9 and SLC36A1 mRNA expressions, AAAs supplementation significantly decreased mucosal amino acid (AA) concentrations of methionine (Met), Arg, Ala, and Tyr, etc. (P < 0.05). And the interaction between AAAs supplementation and LPS challenge significantly altered the expressions of SLC36A1 and SLC38A9 mRNA (P < 0.05). Together, these findings indicated that AAAs supplementation promoted the AAs absorption and utilization in the small intestine of piglets and increased the mRNA expressions of SLC transports to meet the high demands for specific AAs in response to inflammation and immune response.


2000 ◽  
Vol 167 (2) ◽  
pp. 247-252 ◽  
Author(s):  
H Wang ◽  
H Wolosker ◽  
J Pevsner ◽  
SH Snyder ◽  
DJ Selkoe

Little evidence is available for the physiological function of D-amino acids in species other than bacteria. Here we demonstrate that naturally occurring freed -aspartate (D-Asp) is present in all magnocellular neurons of rat hypothalamus. The levels of this naturally occurring D-amino acid were elevated during lactation and returned to normal thereafter in the magnocellular neurosecretory system, which produces oxytocin, a hormone responsible for milk ejection during lactation. Intraperitoneal injections of D-Asp reproducibly increased oxytocin gene expression and decreased the concentration of circulating oxytocin in vivo. Similar changes were observed in the vasopressin system. These results provide evidence for the role(s) of naturally occurring free D-Asp in mammalian physiology. The findings argue against the conventional concept that only L-stereoisomers of amino acids are functional in higher species.


2018 ◽  
Vol 120 (12) ◽  
pp. 1321-1331 ◽  
Author(s):  
Hongnan Liu ◽  
Bie Tan ◽  
Bo Huang ◽  
Jianjun Li ◽  
Jing Wang ◽  
...  

AbstractCa2+-sensing receptor (CaSR) represents a potential therapeutic target for inflammatory bowel diseases and strongly prefers aromatic amino acid ligands. We investigated the regulatory effects of dietary supplementation with aromatic amino acids – tryptophan, phenylalanine and tyrosine (TPT) – on the CaSR signalling pathway and intestinal inflammatory response. The in vivo study was conducted with weanling piglets using a 2 × 2 factorial arrangement in a randomised complete block design. Piglets were fed a basal diet or a basal diet supplemented with TPT and with or without inflammatory challenge. The in vitro study was performed in porcine intestinal epithelial cell line to investigate the effects of TPT on inflammatory response using NPS-2143 to inhibit CaSR. Dietary supplementation of TPT alleviated histopathological injury and decreased myeloperoxidase activity in intestine challenged with lipopolysaccharide. Dietary supplementation of TPT decreased serum concentration of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-12, granulocyte-macrophage colony-stimulating factor, TNF-α), as well as the mRNA abundances of pro-inflammatory cytokines in intestine but enhanced anti-inflammatory cytokines IL-4 and transforming growth factor-β mRNA levels compared with pigs fed control diet and infected by lipopolysaccharide. Supplementation of TPT increased CaSR and phospholipase Cβ2 protein levels, but decreased inhibitor of NF-κB kinase α/β and inhibitor of NF-κB (IκB) protein levels in the lipopolysaccharide-challenged piglets. When the CaSR signalling pathway was blocked by NPS-2143, supplementation of TPT decreased the CaSR protein level, but enhanced phosphorylated NF-κB and IκB levels in IPEC-J2 cells. To conclude, supplementation of aromatic amino acids alleviated intestinal inflammation as mediated through the CaSR signalling pathway.


2018 ◽  
Vol 9 (8) ◽  
pp. 4143-4152 ◽  
Author(s):  
Shuai Chen ◽  
Meiwei Wang ◽  
Lanmei Yin ◽  
Wenkai Ren ◽  
Peng Bin ◽  
...  

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is strongly associated with intestinal immunity and the microbiome.


2020 ◽  
Vol 21 (12) ◽  
pp. 4211 ◽  
Author(s):  
Valeria De Pasquale ◽  
Marianna Caterino ◽  
Michele Costanzo ◽  
Roberta Fedele ◽  
Margherita Ruoppolo ◽  
...  

Mucopolysaccharidoses (MPSs) are inherited disorders of the glycosaminoglycan (GAG) metabolism. The defective digestion of GAGs within the intralysosomal compartment of affected patients leads to a broad spectrum of clinical manifestations ranging from cardiovascular disease to neurological impairment. The molecular mechanisms underlying the progression of the disease downstream of the genetic mutation of genes encoding for lysosomal enzymes still remain unclear. Here, we applied a targeted metabolomic approach to a mouse model of PS IIIB, using a platform dedicated to the diagnosis of inherited metabolic disorders, in order to identify amino acid and fatty acid metabolic pathway alterations or the manifestations of other metabolic phenotypes. Our analysis highlighted an increase in the levels of branched-chain amino acids (BCAAs: Val, Ile, and Leu), aromatic amino acids (Tyr and Phe), free carnitine, and acylcarnitines in the liver and heart tissues of MPS IIIB mice as compared to the wild type (WT). Moreover, Ala, Met, Glu, Gly, Arg, Orn, and Cit amino acids were also found upregulated in the liver of MPS IIIB mice. These findings show a specific impairment of the BCAA and fatty acid catabolism in the heart of MPS IIIB mice. In the liver of affected mice, the glucose-alanine cycle and urea cycle resulted in being altered alongside a deregulation of the BCAA metabolism. Thus, our data demonstrate that an accumulation of BCAAs occurs secondary to lysosomal GAG storage, in both the liver and the heart of MPS IIIB mice. Since BCAAs regulate the biogenesis of lysosomes and autophagy mechanisms through mTOR signaling, impacting on lipid metabolism, this condition might contribute to the progression of the MPS IIIB disease.


Cell Reports ◽  
2020 ◽  
Vol 33 (1) ◽  
pp. 108229
Author(s):  
Emilie Viennois ◽  
Alexis Bretin ◽  
Philip E. Dubé ◽  
Alexander C. Maue ◽  
Charlène J.G. Dauriat ◽  
...  

1984 ◽  
Vol 4 (2_suppl) ◽  
pp. 121-124 ◽  
Author(s):  
Ramesh Khanna ◽  
George Wu ◽  
Helen Rodella ◽  
Dimitrios G. Oreopoulos

A number of CAPD patients may develop malnutrition due to multiple causes. Average daily amino acid loss during CAPD was 2 gm per day. Serum concentrations of almost all essential and non essential amino acids were significantly lower than controls. Amino acid containing solution is an effective osmotic agent and at the same time is suitable for nutritional supplementation. Use of this solution up to 4 weeks did not lead to any abnormal accumulation of amino acids and patient appeared to tolerate it well. A number of CAPD patients may develop malnutrition which appears to be brought about by a combination of decreased appetite, and increased nutrient loss in the dialysate. In a group of 13 patients whose daily protein and caloric intakes at the beginning of CAPD were 1.5 9 per kg, and 35 Kcal/kg respectively, intakes decreased spontaneously after one year on CAPD even though they were being advised during their clinic visits to maintain initial protein and caloric intakes (1). Reduced intakes appear to result from decreased appetite and a feeling of fullness, although these factors are difficult to evaluate quantitatively. To gain information as to the etiology of appetite suppression during CAPD, we performed CAPD in nonuremic rabbits.


2003 ◽  
Vol 98 (3) ◽  
pp. 729-733 ◽  
Author(s):  
Yi Feng ◽  
Minglei Cui ◽  
William D. Willis

Background Gabapentin has recently been used clinically as an antihyperalgesic agent to treat certain neuropathic pain states. The aim of this study is to test whether gabapentin is able to inhibit responses to peritoneal irritation-induced visceral pain and to examine the effect of gabapentin on spinal cord amino acid release. Methods The acetic acid-induced writhing assay was used in rats to determine the degree of antinociception. The rats received an intraperitoneal injection of acetic acid 40 min after intraperitoneal administration of vehicle or gabapentin (50, 100, or 200 mg/kg). Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space in anesthetized rats. Acetic acid-induced release of amino acids into the dialysate, including glutamate, aspartate, serine, glutamine, and glycine, following intraperitoneal injection of acetic acid was evaluated by measurements of changes in the concentrations of these amino acids. The effects of pretreatment with saline or gabapentin (100 mg/kg intraperitoneal) on amino acid release were compared. Results Gabapentin reduced writhing responses in a dose-related fashion. Dialysate concentrations of glutamate, aspartate, and serine increased significantly following intraperitoneal injection of acetic acid, while glutamine and glycine concentrations were not increased significantly. When compared to saline-treated rats, animals pretreated with 100 mg/kg gabapentin showed suppression of the acetic acid-induced increases in glutamate, aspartate, and serine concentrations. Conclusions These data demonstrate that gabapentin effectively inhibits acetic acid-induced nociception, and the antinociceptive effect of gabapentin correlates with the suppression of noxious-evoked release of excitatory amino acids in the spinal cord.


2008 ◽  
Vol 295 (1) ◽  
pp. G1-G6 ◽  
Author(s):  
Jamilur R. Talukder ◽  
Ramesh Kekuda ◽  
Prosenjit Saha ◽  
Uma Sundaram

In a rabbit model of chronic intestinal inflammation, we previously demonstrated inhibition of neutral Na-amino acid cotransport. The mechanism of the inhibition was secondary to a decrease in the affinity for amino acid rather than the number of cotransporters. Since leukotriene (LT)D4 is known to be elevated in enterocytes during chronic intestinal inflammation, we used rat intestinal epithelial cell (IEC-18) monolayers to determine the mechanism of regulation of Na-alanine cotransport (alanine, serine, cysteine transporter 1: ASCT1) by LTD4. Na-alanine cotransport was inhibited by LTD4 in IEC-18 cells. The mechanism of inhibition of ASCT1 (solute carrier, SLC1A4) by LTD4 is secondary to a decrease in the affinity of the cotransporter for alanine without a significant change in cotransporter numbers and is not secondary to an alteration in the Na+ extruding capacity of the cells. Real-time quantitative PCR and Western blot analysis results indicate that ASCT1 message and protein levels are also unchanged in LTD4-treated IEC-18 cells. These results indicate that LTD4 inhibits Na-dependent neutral amino acid cotransport in IEC. The mechanism of inhibition is secondary to a decrease in the affinity for alanine, which is identical to that seen in villus cells from the chronically inflamed rabbit small intestine, where LTD4 levels are significantly increased.


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