scholarly journals Involvement of calcium-sensing receptor activation in the alleviation of intestinal inflammation in a piglet model by dietary aromatic amino acid supplementation

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.

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245739
Author(s):  
Inês Vieira da Silva ◽  
Bárbara P. Soares ◽  
Catarina Pimpão ◽  
Rui M. A. Pinto ◽  
Teresa Costa ◽  
...  

The regulation of glycerol permeability in the gastrointestinal tract is crucial to control fat deposition, lipolysis and gluconeogenesis. Knowing that the amino acid glutamine is a physiological regulator of gluconeogenesis, whereas cystine promotes adiposity, herein we investigated the effects of dietary supplementation with glutamine and cystine on the serum biochemical parameters of piglets fed on amino acid-enriched diets, as well as on the transcriptional profile of membrane water and glycerol channels aquaporins (AQPs) in the ileum portion of the small intestine and its impact on intestinal permeability. Twenty male piglets with an initial body weight of 8.8 ± 0.89 kg were allocated to four dietary treatments (n = 5) and received, during a four week-period, a basal diet without supplementation (control) or supplemented with 8 kg/ton of glutamine (Gln), cystine (Cys) or the combination of the two amino acids in equal proportions (Gln + Cys). Most biochemical parameters were found improved in piglets fed Gln and Cys diet. mRNA levels of AQP3 were found predominant over the others. Both amino acids, individually or combined, were responsible for a consistent downregulation of AQP1, AQP7 and AQP10, without impacting on water permeability. Conversely, Cys enriched diet upregulated AQP3 enhancing basolateral membranes glycerol permeability and downregulating glycerol kinase (GK) of intestinal cells. Altogether, our data reveal that amino acids dietary supplementation can modulate intestinal AQPs expression and unveil AQP3 as a promising target for adipogenesis regulation.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ali Olfati ◽  
Seyed Majid Hosseini

Abstract Salmonella Typhimurium (S. Typhimurium) causes inflammation and has adverse effects on the growth of broiler chicks. Meanwhile, plant derivations improve the growth performance and decrease inflammation, but they do not have enough stability. Encapsulation of essential oils is a new strategy for decreasing their instability. This study was conducted to investigate the effects of dietary supplementation of encapsulated Thyme essential oil (ETEO) on growth, inflammatory cytokines, and amino acid profiles of broiler chicks challenged with S. Typhimurium. Three hundred one-d-old broiler chicks were assigned into 6 groups, and 5 replications per group. The broiler chicks (3 groups) were challenged with S. Typhimurium, on day 21 and birds received basal diet (positive control), encapsulated Thyme (P-ETEO), and non-capsulated Thyme (P-NETEO), while other groups received the same diets, but under normal as a negative control, encapsulated Thyme (N-ETEO) and non-capsulated Thyme (N-NETEO). Growth performance, pro-inflammatory cytokines, and serum amino acid profiles were assessed on day 42. The challenged birds in positive control showed lower growth performance, higher concentration for inflammatory cytokines, and disturbed blood serum concentrations for amino acid profiles compared to the negative control (P<0.05). The result showed that dietary supplementation of the ETEO could improve growth performance and amino acid profiles, and also decrease inflammatory responses (P<0.05). In sum, S. Typhimurium had negative effects on growth, immunity, and inflammation, but dietary inclusion of the ETEO could decrease its negative effects.


Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3091
Author(s):  
Omar A. Ahmed-Farid ◽  
Ayman S. Salah ◽  
Mohamed Abdo Nassan ◽  
Mahmoud S. El-Tarabany

Guanidinoacetic acid (GA) is a natural precursor of creatine in the body and is usually used to improve the feed conversion and cellular energy metabolism of broiler chickens. The objective was to elucidate the effect of dietary supplementation of GA on carcass yield, muscle amino acid profile, and concentrations of brain neurotransmitters in laying hens. In total, 128 72-week-old ISA Brown laying hens were assigned to four equal groups (32 birds, eight replicates per group). The control group (T1) was fed a basal diet with no supplements, while the other experimental groups were fed a basal diet supplemented with 0.5 (T2), 1.0 (T3), and 1.5 (T4) g GA kg−1 diet. The T3 and T4 groups showed higher hen-day egg production and carcass yield compared to the control group (p = 0.016 and 0.039, respectively). The serum creatine level increased linearly with the increased level of dietary GA (p = 0.007). Among the essential amino acids of breast muscle, a GA-supplemented diet linearly increased the levels of leucine, isoleucine, phenylalanine, methionine, and threonine in the breast (p = 0.003, 0.047, 0.001, 0.001, and 0.015, respectively) and thigh (p = 0.026, 0.001, 0.020, 0.009, and 0.028, respectively) muscles. GA supplementation linearly reduced the level of brain serotonin compared to the control group (p = 0.010). Furthermore, supplementation of GA in the diet of laying hens linearly increased the level of brain dopamine (p = 0.011), but reduced the level of brain Gamma-aminobutyric acid (p = 0.027). Meanwhile, the concentration of brain nitric oxide did not differ between the experimental groups (p = 0.080). In conclusion, the dietary supplementation of GA may improve the carcass yield and levels of essential amino acids in the breast muscles, as well as the brain neurotransmitters in aged laying hens.


2018 ◽  
Author(s):  
Nidhi Gour ◽  
Bharti Koshti ◽  
Chandra Kanth P. ◽  
Dhruvi Shah ◽  
Vivek Shinh Kshatriya ◽  
...  

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. To get insights into the structure formation, thioflavin T and Congo red binding assays were done which revealed that aggregates may not have amyloid like characteristics. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. The cytotoxicity assays of cysteine and methionine structures were performed on Human Neuroblastoma IMR-32 cells which suggested that aggregates are not cytotoxic in nature and thus, may not have amyloid like etiology. The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Carolyn A. Harris ◽  
Diego M. Morales ◽  
Rooshan Arshad ◽  
James P. McAllister ◽  
David D. Limbrick

Abstract Background Approximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus. Methods Using multiplex ELISA, this study examined shunt failure through the CSF protein concentration profiles of select pro-inflammatory and anti-inflammatory cytokines, as well as select MMPs. Interdependencies such as the past number of previous revisions, length of time implanted, patient age, and obstruction or non-obstruction revision were examined. The pro-inflammatory cytokines were IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12, IL-17, TNF-α, GM-CSF, IFN-γ. The anti-inflammatory cytokines were IL-4 and IL-10, and the MMPs were MMP-2, MMP-3, MMP-7, MMP-9. Protein concentration is reported as pg/mL for each analyte. Results Patient CSF was obtained at the time of shunt revision operation; all pediatric (< 18), totaling n = 38. IL-10, IL-6, IL-8 and MMP-7 demonstrated significantly increased concentrations in patient CSF for the non-obstructed subgroup. Etiological examination revealed IL-6 was increased in both obstructed and non-obstructed cases for PHH and congenital hydrocephalic patients, while IL-8 was higher only in PHH patients. In terms of number of past revisions, IL-10, IL-6, IL-8, MMP-7 and MMP-9 progressively increased from zero to two past revisions and then remained low for subsequent revisions. This presentation was notably absent in the obstruction subgroup. Shunts implanted for three months or less showed significantly increased concentrations of IL-6, IL-8, and MMP-7 in the obstruction subgroup. Lastly, only patients aged six months or less presented with significantly increased concentration of IL-8 and MMP-7. Conclusion Non-obstructive cases are reported here to accompany significantly higher CSF cytokine and MMP protein levels compared to obstructive cases for IL-10, IL-6, IL-8, MMP-7 and MMP-9. A closer examination of the definition of obstruction and the role neuroinflammation plays in creating shunt obstruction in hydrocephalic patients is suggested.


1984 ◽  
Vol 62 (5) ◽  
pp. 276-279 ◽  
Author(s):  
C. H. Lin ◽  
W. Chung ◽  
K. P. Strickland ◽  
A. J. Hudson

An isozyme of S-adenosylmethionine synthetase has been purified to homogeneity by ammonium sulfate fractionation, DEAE-cellulose column chromatography, and gel filtration on a Sephadex G-200 column. The purified enzyme is very unstable and has a molecular weight of 120 000 consisting of two identical subunits. Amino acid analysis on the purified enzyme showed glycine, glutamate, and aspartate to be the most abundant and the aromatic amino acids to be the least abundant. It possesses tripolyphosphatase activity which can be stimulated five to six times by S-adenosylmethionine (20–40 μM). The findings support the conclusion that an enzyme-bound tripolyphosphate is an obligatory intermediate in the enzymatic synthesis of S-adenosylmethionine from ATP and methionine.


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2416
Author(s):  
Reza Barekatain ◽  
Tristan Chalvon-Demersay ◽  
Clive McLaughlan ◽  
William Lambert

Two experiments were conducted to investigate the effect of arginine (Arg); the combination of Arg and glutamine (Gln); as well as an amino acid-based solution (MIX) containing Arg, Gln, threonine (Thr), and grape extract, on performance, intestinal permeability, and expression of selected mechanistic genes. Using 240 male Ross 308 off-sex broiler chickens, four experimental treatments were replicated six times with 10 birds per replicate. The experimental treatments included 5 g/kg Arg, 2.5 g/kg Arg and 2.5 g/kg Gln, and 1 g/kg MIX added to a basal diet as control. In the second study, the four dietary treatments were then given to 24 birds with or without a synthetic glucocorticoid, dexamethasone (DEX), as a gut dysfunction model. Feed conversion ratio was improved by all the supplemented treatments from day 7 to 35 of age (p < 0.001). DEX injections increased (p < 0.001) the intestinal permeability in all treatments, which tended to be reversed by Arg or MIX. Additional Arg, Arg-Gln, and MIX suppressed (p < 0.05) the overexpression of IL-1β generated by DEX. Feeding birds with MIX treatment increased (p < 0.05) expression of SGLT-1 and glutathione synthetase. In conclusion, tested amino acid supplements were effective in improving feed efficiency and restraining intestinal inflammation caused by DEX through IL-1β pathway.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yung Jae Kim ◽  
Byoung Jun Choi ◽  
Si Hyoung Park ◽  
Han Byeol Lee ◽  
Ji Eun Son ◽  
...  

Peptidoglycan (PG) hydrolases play important roles in various aspects of bacterial physiology, including cytokinesis, PG synthesis, quality control of PG, PG recycling, and antibiotic resistance. However, the regulatory mechanisms of their expression are poorly understood. In this study, we have uncovered novel regulatory mechanisms of the protein levels of the synthetically lethal PG endopeptidases MepS and MepM, which are involved in PG synthesis. A mutant defective for both MepS and MepM was lethal in an amino acid-rich medium, whereas it exhibited almost normal growth in a minimal medium, suggesting the expendability of MepS and MepM in a minimal medium. Protein levels of MepS and MepM dramatically decreased in the minimal medium. Although MepM was revealed as a substrate of Prc, a periplasmic protease involved in the proteolysis of MepS, only the decrease in the MepS level in the minimal medium was affected by the prc depletion. Phenotypic and biochemical analyses showed that the presence of aromatic amino acids in the medium induced the accumulation of MepS, but not MepM, while the presence of glutamate increased the level of MepM, but not MepS. Together, these results demonstrate that the protein levels of the two major PG endopeptidases are regulated in an amino acid availability-dependent manner, but their molecular mechanisms and signaling are significantly distinct.


2019 ◽  
Vol 127 (10) ◽  
pp. 541
Author(s):  
В.С. Горелик ◽  
М.Ф. Умаров ◽  
Ю.П. Войнов

AbstractRaman spectra of tryptophan and tyrosine polycrystals have been analyzed in a wide spectral range by fiber-optic spectroscopy. The Raman spectra have been recorded with a BWS465-785H spectrometer in the spectral range of 0–2700 cm^–1 using a 785-nm cw laser as an excitation source. Parameters of the Raman spectra are compared for three crystalline phase modifications of aromatic amino acids: left-handed, right-handed, and racemic phase. The presence of strong Raman satellites, the characteristics of which change depending on the type of the chiral phase state of amino acid, is found in the low-frequency Raman spectra of tryptophan and tyrosine amino acid lattices. The results obtained can be used for monitoring the chiral purity of bioactive preparations containing amino acids.


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