Academic literature on the topic 'Methionine supplementation'

This study investigated the egg production pattern at the onset of lay until peak production in Japanese quails (Coturnix coturnix japonica) fed diet supplemented with betaine and methionine. Three hundred laying quails were randomly allocated to three groups of supplementations with 5 replicates of 20 quails. The three groups of treatments included basal diet (Control) or basal diet supplemented with 1.2 g betaine and 1.2 g methionine per kg diet. During onset of lay until 50% egg production (6 to 9 weeks of age), all groups were fed a basal diet, while the supplements were applied after 9 weeks. The egg production data were analyzed with analysis of variance and followed by Duncan’s test for significant results. During week 6 to 9, all groups of quails generated similar egg production since they received the basal diet. On the later phase, supplementation of betaine and methionine enhanced average weekly egg production (P<0.05) starting from week 10 compared with those without supplementation. The egg production curves indicated that production rapidly reached 60% soon after the onset of lay. Then, egg production rose sharply and reached the peaks of more than 80%, indicating good egg production patterns. Supplementation of betaine and methionine enhanced the average overall and peak production (P<0.01) without affecting the age at peak production. In addition, there were positive correlations between average of overall production and peak production of all treatments. It can be concluded that supplementation of betaine and methionine enhanced egg production in quails.

Methionine restriction and selenium supplementation are recommended because of their health benefits. As a major nutrient form in selenium supplementation, selenomethionine shares a similar biological process to its analog methionine. However, the outcome of selenomethionine supplementation under different methionine statuses and the interplay between these two nutrients remain unclear. Therefore, this study explored the metabolic effects and selenium utilization in HepG2 cells supplemented with selenomethionine under deprived, adequate, and abundant methionine supply conditions by using nuclear magnetic resonance-based metabolomic and molecular biological approaches. Results revealed that selenomethionine promoted the proliferation of HepG2 cells, the transcription of selenoproteins, and the production of most amino acids while decreasing the levels of creatine, aspartate, and nucleoside diphosphate sugar regardless of methionine supply. Selenomethionine substantially disturbed the tricarboxylic acid cycle and choline metabolism in cells under a methionine shortage. With increasing methionine supply, the metabolic disturbance was alleviated, except for changes in lactate, glycine, citrate, and hypoxanthine. The markable selenium accumulation and choline decrease in the cells under methionine shortage imply the potential risk of selenomethionine supplementation. This work revealed the biological effects of selenomethionine under different methionine supply conditions. This study may serve as a guide for controlling methionine and selenomethionine levels in dietary intake.

This study was aimed at investigating the effects of quercetin on mRNA expression and activity of critical enzymes in homocysteine metabolism in rats fed a methionine-enriched diet. Rats were fed for 6 weeks the following diets, that is, control, 0.5% quercetin, 1.0% methionine, and 1.0% methionine plus 0.5% quercetin diets. Serum homocysteine was significantly increased after methionine treatment and decreased after the addition of quercetin. The mRNA expression of methionine synthase was significantly increased after methionine or methionine plus quercetin supplementation, while its enzymatic activity was significantly increased after methionine plus quercetin supplementation. The mRNA expression and enzymatic activity of cystathionineβ-synthase and cystathionineγ-lyase were upregulated after quercetin, methionine, or quercetin plus methionine treatment and a more significant increase was observed for hepatic cystathionineβ-synthase in the methionine plus quercetin treated rats, suggesting an interaction between methionine and quercetin. Meanwhile, hepatic ratio of S-adenosylmethionine to S-adenosylhomocysteine was significantly decreased in response to methionine supplementation and normalized after the addition of quercetin. It is concluded that quercetin reduces serum homocysteine by increasing remethylation and transsulfuration of homocysteine in rats exposed to a methionine-enriched diet.

The aim of the present study was to evaluate the effects of heat stress (HS) and methionine supplementation on the markers of stress and on the gene expression levels of uncoupling proteins (UCP), betaine–homocysteine methyltransferase (BHMT), cystathionine β-synthase (CBS), glutathione synthetase (GSS) and glutathione peroxidase 7 (GPx7). Broilers from 1 to 21 d and from 22 to 42 d of age were divided into three treatment groups related to methionine supplementation: without methionine supplementation (MD); recommended level of methionine supplementation (DL1); excess methionine supplementation (DL2). The broilers were either kept at a comfortable thermal temperature or exposed to HS (38°C for 24 h). During the starter period, we observed the effects of the interaction between diet and environment on the gene expression levels of UCP, BHMT and GSS. Higher gene expression levels of UCP and BHMT were observed in broilers that were maintained at thermal comfort conditions and received the MD diet. HS broilers fed the DL1 and DL2 diets had the highest expression level of GSS. The expression levels of the CBS and GPx7 genes were influenced by both the environment and methionine supplementation. During the grower period, the gene expression levels of BHMT, CBS, GSS and GPx7 were affected by the diet × environment interaction. A higher expression level of BHMT was observed in broilers maintained at thermal comfort conditions and on the MD diet. HS induced higher expression levels of CBS, GSS and GPx7 in broilers that received the DL1 and DL2 diets. The present results suggest that under HS conditions, methionine supplementation could mitigate the effects of stress, since methionine contributed to the increased expression levels of genes related to antioxidant activity.

An elevated plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease and for having offspring with a neural-tube defect. Folate is a methyl donor in the remethylation of homocysteine into methionine. Although folic acid supplementation decreases tHcy concentrations, effects of folic acid supplementation on plasma methionine concentrations are unclear. There is also concern that folic acid supplementation negatively affects vitamin B12 status. We studied effects of low-dose folic acid supplementation on methionine and vitamin B12 concentrations in plasma. We also investigated whether baseline plasma methionine and tHcy concentrations correlated with the baseline folate and vitamin B12 status. For a period of 4 weeks, 144 young women received either 500 μg folic acid each day, or 500 μg folic acid and placebo tablets on alternate days, or a placebo tablet each day. Plasma methionine, tHcy and plasma vitamin B12 concentrations were measured at start and end of the intervention period. Folic acid supplementation had no effect on plasma methionine or plasma vitamin B12 concentrations although it significantly decreased tHcy concentrations. Plasma methionine concentrations showed no correlation with either tHcy concentrations (Spearman rs - 0·01, P = 0·89), or any of the blood vitamin variables at baseline. Baseline tHcy concentrations showed a slight inverse correlation with baseline concentrations of plasma vitamin B12 (rs - 0·25, P < 0·001), plasma folate (rs - 0·24, P < 0·01) and erythrocyte folate (rs - 0·19, P < 0·05). In conclusion, low-dose folic acid supplementation did not influence plasma methionine or plasma vitamin B12 concentrations. Furthermore, no correlation between plasma methionine concentrations and the blood folate and vitamin B12 status was shown.

The purpose of this study is to assess the optimization of fermentation process by adding a minerals and amino acids so that the potential of protein of Concentrate Protein-Jatropha seed cake (CP-JSC) can be optimally used as a substitute for soybean meal. The method used was completely randomized design. The treatment consisted of F1: Fermentation CP-BBJ + methionine-lysine (0.25%: 0.25%), F2: Fermentation CP-JSC + methionine-lysine (0.5%: 0.5%), F3: F1 + 0.45% Dicalsium Phosphate, F4: F2 + 0.45% Dicalsium Phosphate. Each treatment was repeated four times, When treatment significantly continued by Least Significant Difference (LSD), variables observed are the levels of antinutrients (phorbolester, antitrypsin), the levels of nutrients (fat, protein, crude fiber, Ca, P and gross energy) and amino acid. Results of analysis of variance showed that the addition of amino acids and minerals Ca, P in the fermentation process was highly significant effect on the levels of crude fiber and phosphorus (P <0.01) and significantly affected the gross energy content of CP-JSC post-fermentation (P <0.05). Dry matter, crude protein, crude lipid and calcium are not affected by supplementation of methionine and lysine as well as calcium and phosphorus. Supplementation of methionine and lysine in the fermentation substrate showed good levels of essential amino acids and non essential higher than previous studies although not statistically significant (P> 0.05). While the levels obtained phorbolester range of 0.055% - 0.08%. It was concluded that the optimization of fermentation can be done without adding the amino acid supplementation of minerals calcium and phosphorus. Supplementation significantly affect a significant increase or decrease in some nutrients (crude fiber, gross energy, phosphor) and capable of suppressing a decrease in amino acids. Supplementation of amino acids Lysine and Methionin 0.05% is the best treatment.

Rate of degradation of hay was studied, using the nylon-bag technique, in 2 cows given a basal diet without (controls) or with a liquid methionine supplement (LiquimethReg.) or a protected methionine supplement (MepronReg.) providing methionine 25 g daily. After 24 and 48 h incubation methionine supplementation significantly increased degradation of DM, organic matter and cell wall constituents compared with controls. Degradability of crude protein (CP) was significantly increased by methionine supplementation, and degradability was affected by type of supplement with degradability of CP greater with the liquid methionine supplement than with the protected methionine supplement. (Abstract retrieved from CAB Abstracts by CABI’s permission)

Sarcopenia is a condition that is most common in aged animals, and is characterized by the loss of skeletal muscle mass and integrity, and can lead to physical disability and poor quality of life. Since skeletal muscle protein synthesis can be limited by the availability of amino acids, supplementation of limiting amino acids to ameliorate the progression of sarcopenia has become a topic of interest in companion animal research. Although there is some data to support the idea that amino acid supplementation improves maintenance of muscle mass in aged horses, the cellular mechanisms behind that improvement have yet to be elucidated. Therefore, the objective of this study was to examine the effect of amino acid supplementation in aged horses on markers of whole body and muscle protein metabolism. In a cross-over design, six old horses were studied while receiving each of three treatments in a replicated Latin square design. For all three treatments, horses received 1.8% BW/d of timothy hay cubes and 0.5% BW/d of experimental concentrate. The three treatments included a control (CON) treatment concentrate that was designed to meet all requirements of mature horses when fed in combination with the timothy hay cubes, and two supplemented concentrates, LYS/THR with additional lysine and threonine (40 mg/kg BW/d and 31 mg/kg BW/d, respectively), and LYS/THR/MET with additional lysine, threonine, and methionine (40 mg/kg BW/d, 31 mg/kg BW/d and 11mg/kg BW/d respectively). In each 15 d period, following a 9-day adaptation, horses were fitted with a collection harness, and total urine and feces were collected for 72 hours for assessment of nitrogen balance and creatinine output. Blood samples were taken directly before feeding and 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-feeding for analysis of plasma urea nitrogen (PUN), glucose, insulin, and plasma amino acid concentrations. Muscle biopsy samples were taken for analysis of proteins in the mTOR pathway. Additionally, horses underwent stable isotope infusion procedures, and comparisons of phenylalanine kinetics were used to determine whole-body rates of protein synthesis and degradation. There was no significant effect of treatment on creatinine output (P=0.58), relative abundance of proteins in the mTOR pathway (P>0.05), nitrogen retention (P=0.70), or phenylalanine kinetics (P>0.05). PUN concentrations were significantly (P=0.0058) higher for LYS/THR and LYS/THR/MET than for CON. Atrogin-1 activation was significantly higher for the pre-feeding CON sample compared to the post-feeding CON sample. Lack of significant difference in creatinine output suggests that there were not significant differences in muscle mass between treatments. Lack of significant differences in mTOR protein activation suggests that amino acid supplementation did not result in improvements in protein synthesis. Lack of significant differences in nitrogen retention and phenylalanine kinetics suggests that whole-body protein metabolism was not improved. Additionally, higher PUN concentrations in the supplemented diets suggests that the supplemented amino acids being provided were catabolized. However, increased activation of Atrogin-1 in the pre-feeding CON samples, but not the pre-feeding samples of supplemented treatments, suggests amino acid supplementation may have reduced protein degradation in the post-absorptive state. Data from the present study suggests that amino acid availability may not have been limiting protein synthesis in the sedentary aged horses in the present study.

Improper acquisition of DNA methylation patterns during the fetal period in germ cells of male mice is associated with impaired meiosis and infertility. MTHFR is a key folate pathway enzyme involved in providing methyl groups for DNA methylation. The goal of these studies was to evaluate DNA methylation patterns in spermatogonia from mice heterozygous for a targeted deletion in Mthfr (Mthfr+/-) as compared to those of their wildtype, Mthfr+/+, littermates. DNA methylation patterns were similar at imprinted genes and intergenic sites across chromosome 9 in neonatal spermatogonia of Mthfr+/+ and Mthfr+/- mice. We then established spermatogonial stem cell (SSC) cultures from Mthfr+/+ and Mthfr+/- mice to examine the stability of DNA methylation patterns over time in culture and determine whether methionine supplementation could restore any DNA methylation defects caused by MTHFR haplosufficiency. There were no differences detected between early and late passages, suggesting DNA methylation patterns in SSC clusters are generally stable in culture. Cultured SSC clusters treated with 20-fold normal medium methionine concentrations showed an overall increase in the levels of DNA methylation across chromosome 9, indicating DNA methylation can be perturbed in culture. Additionally, Mthfr+/- SSC clusters cultured in varying concentrations of methionine demonstrated a significantly increased variance of DNA methylation at multiple loci across chromosome 9 compared to Mthfr+/+ SSC clusters treated the same way. Together our results provide evidence that DNA methylation patterns of SSC clusters are stable in culture but can be perturbed by altered methionine and MTHFR levels.
L'acquisition inexacte de patrons de méthylation d'ADN des cellules germinales pendant la période fœtale chez la souris mâle est associée à des désordres de méiose et d'infertilité. L'enzyme MTHFR joue un rôle clé dans le processus de méthylation d'ADN puisqu'elle est impliquée dans une cascade produisant les groupements méthyles nécessaires à la réaction. L'objectif des travaux présentés dans ce mémoire était d'évaluer les profiles de méthylation d'ADN dans les spermatogonies provenant de souris hétérozygotes pour une suppression ciblée de Mthfr (Mthfr+/-), en comparaison avec celles découlant des compagnons de type sauvage de la même portée (Mthfr +/+). Nous avons déterminé que dans les spermatogonies néonatales de souris Mthfr+/+ et Mthfr+/- les patrons de méthylation sont demeurés similaires au niveau des gènes à empreinte ainsi qu'à divers sites intergéniques retrouvés à travers le chromosome 9. Subséquemment nous avons établi un système de culture de cellules souches spermatogoniales (SSC) à partir de souris Mthfr+/+ et Mthfr+/- afin d'examiner la stabilité des profiles de méthylation en culture et de déterminer si un supplément de méthionine peut restaurer un dérèglement de méthylation d'ADN causé par une haploinsuffisance de MTHFR. La période de culture (nombre de passages faible vs élevé) n'a nullement altérée les patrons de méthylation d'ADN, ce qui suggère que cette modification épigénétique est globalement très stable dans les SSCs en culture. Le traitement de ces même SSCs avec un milieu 20 fois plus élevé en méthionine occasionne par contre une augmentation des niveaux globaux de méthylation d'ADN à travers le chromosome 9, démontrant que cette modification post-traductionnelle peut être perturbée en culture. De plus, la culture des SSCs Mthfr+/- dans diverses concentrations de methionine démontre une augmentation significative de la variance des niveaux de méthylation d'ADN pour une multitude de loci à travers le chromosome 9 comparativement aux SSCs Mthfr+/+ soumis aux mêmes traitements. Ensemble, nos résultats suggèrent que les patrons de méthylation d'ADN des SSCs sont normalement stables en culture mais peuvent cependant être perturbés par les niveaux de méthionine et MTHFR.

A metionina é doadora de grupos metil para metilação do DNA, processo responsável por modificações da expressão gênica. Diante da importância da metionina para o crescimento e desenvolvimento normais, variações desse aminoácido na dieta podem alterar a estabilidade do DNA. O objetivo desse trabalho foi avaliar o efeito de dietas deficiente e suplementada em metionina sobre a instabilidade genômica e o estresse oxidativo em camundongos e suas mães tratadas durante gestação e lactação e destas também foi realizada a expressão de RNAm de Mat1a, Bhmt e Cbsdas vias de transmetilação, remetilação e transsulfuração da metionina, respectivamente, em fígado. As fêmeas foram divididas nos grupos de dietas de metionina (controle, 0,3% DL-metionina; suplementado, 2,0%; e deficiente 0%) até o fim da lactação (10 semanas) e, para cada grupo de fêmeas, os filhotes foram subdivididos e também receberam essas dietas durante 18 semanas após desmame. Foram avaliados o consumo de ração, massa corpórea e massa relativa de fígado e rinse a taxa de sobrevivência dos filhotes. Também foram realizadas a avaliação da peroxidação lipídica (quantificação das substâncias reativas ao ácido tiobarbitúrico, TBARS), da quantificação de glutationa (GSH)e da atividade da catalase, da instabilidade genômica (ensaio do cometa) e a análise do RNAm deMat1a, BhmteCbs somente em fígado das fêmeas. A dieta deficiente resultou em menor consumo de ração e massa corpórea em ambas fases e reduziu a sobrevivência dos filhotes que receberam essa dieta.A suplementação reduziu a concentração de TBARS nas fêmeas em ambos tecidos e a deficiência não diferiu. Nos filhotes, a suplementação reduziu a concentração de TBARS em fígado, enquanto que a deficiência aumentou. A suplementação aumentou a concentração de GSH em fígado das fêmeas, assim como a deficiência em rins. Nos filhotes, houve uma inversão de respostas, ou seja, a suplementação reduziu a concentração de GSH em fígado, assim como a deficiência, também observada em rins. Não houve diferença na catalase das fêmeas, mas houve redução em ambos tecidos dos filhotes. A suplementação e a deficiência reduziram os danos ao DNA hepático das fêmeas, mas em rins a suplementação aumentou e a deficiência reduziu. Nos filhotes, a suplementação e a deficiência aumentaram os danos ao DNA em ambos tecidos. A suplementação de metionina em fêmeas não alterou a expressão dos RNAm avaliados e a deficiência reduziu em Cbs somente. Concluiu-se que na fase materna, a suplementação ou a deficiência de metionina não resultou em estresse oxidativo, mas a suplementação reduziu a instabilidade genômica no fígado e aumentou no rim. A deficiência resultou em menor instabilidade nos dois tecidos. Na fase descendente, a suplementação e a deficiência de metionina apresentaram variação de estresse oxidativo em ambos tecidos e também resultaram em maior instabilidade genômica.
Methionine is the main methyl donor for the DNA methylation, a process responsible for gene expression modifications. Since this essential amino acid is required for normal growth and development, variations of this compound in the diet may lead to alterations on DNA stability. Thus, this study aimed to evaluate the effect of deficient and supplemented methionine diets on oxidative stress and genomic instability in mice and their dams treated during pregnancy and lactation, and the expression of Mat1a, Bhmt and Cbs mRNA of transmethylation, remetthylation, and transulfuration pathways, respectively, in dams livers. The dams were divided into three methionine diets groups (control, 0,3% DL-methionine; supplemented, 2,0%; and deficient, 0%) until the end of lactation (10 weeks). For each dams groups, the offspring were subdivided and were also treated with the same diets during 18 weeks after weaning. The parameters evaluated were food intake, body weight, relative liver and kidney weights, and survival of the offspring. Also, it was carried out theevaluation of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), quantification of glutathione (GSH) and catalase activity, and genomic instability (comet assay) in liver and kidneys; andMat1a, Bhmt, and CbsmRNA analysis only in dams liver. The deficient diet resulted in lower food intake and body weights in both phases and reduced the survival of the offspring that were treated with this diet. The supplemented diet reduced the TBARS concentration in both tissues of dams and the deficient diet did not differ. In the offspring, the supplementation reduced liver TBARS, whereas the deficiency raised. The supplementation increased the liver GSH concentration of dams, as well as the deficiency in kidneys. In the offspring, the responses were different; the supplementation reduced the liver GSH, as well as the deficiency, also observed in kidneys. There were no differences of catalase parameter of dams, but there was a reduction in both tissues of the offspring. Both supplementation and deficiency reduced the liver DNA damage of dams, however the supplementation increased and the deficiency reduced the DNA damage of kidneys. In the offspring, both diets increased the DNA damage in both tissues. The methionine supplementation did not differ the mRNA expression and the deficiency only reduced the Cbs, mRNA expression. It was concluded that the methionine supplementation or deficiency did not resulted in oxidative stress in dams, but the supplementation reduced the genomic instability of liver and raised the kidney one. The deficiency resulted in lower genomic instability in both tissues in dams. In the offspring, both methionine supplementation and deficiency presented variation of oxidative stress in both tissues and resulted more genomic instability.

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype which is clinically difficult to treat, due the lack of targeted therapies. The low specificity and high relapse rates associated to cytotoxic chemotherapy have encouraged the use of immunotherapy as an alternative treatment option, however, overall response rates to anti-PD-1 immunotherapy are still low. In order to improve the current TNBC immunotherapy efficacy, we thought to use supplementation of methionine - an amino acid with antioxidant properties - to decrease the tumour immunosuppression and increase anti-tumour T cell response. To test our hypothesis, in vivo supplementation of methionine was combined with anti-PD-1 immunotherapy to treat TNBC-bearing mice. In this master thesis, we show that methionine supplementation improves anti-PD-1 treatment efficacy in E0771 TNBC tumour model by delaying the tumour growth. Furthermore, an accumulation of tumour-infiltrating lymphocytes (TILs), such as CD8 and γδ T cells was observed in anti-PD-1 and methionine treated mice. Analysis of tumour-bearing TCRδKO mice revealed a possible role for γδ T cells in inducing CD8 T cell accumulation within the tumour, since CD8 T cell number was no longer increased upon combined treatment in this mouse strain. Moreover, we observed a decreased frequency of TNFα and IFNγ producing CD8 T cells in anti-PD-1 + methionine treated TCRδKO mice, thus suggesting a key role of γδ T cells in potentiating anti-tumour CD8 T cell responses in the presence of PD-1 inhibitor and methionine. Collectively, the work presented in this thesis showed, for the first time, that methionine supplementation in combination with anti-PD-1 antibody can exert a protective role in tumour immunity. Further studies are required to understand the molecular mechanisms behind this positive effect of methionine supplementation, and to evaluate a potential application of this combination in TNBC patients.

碩士
輔仁大學
食品營養學系
85
The purpose of this study was to investigate the effect of dietary methionine supplementation on glutathione metabolism of rats during long term Se consumption. Male weanling Sprague-Dawley rats were randomly assigned to recive diets containing 3 levels of dietary Se (adequate: 0.1 mg Se/kg diet, moderately high: 3 mg Se/kg diet, high: 5 mg Se/kg diet, as sodium selenite) and 3 levels of dietary methionine supplement (0, 0.3, or 0.6 g Met/100 g diet). Results showed that hepatic and erythrocyte glutathione (GSH) and GSH/GSSG ratio decreased significantly whereas glutathione disulfide (GSSG) increased significantly due to long term excessive Se ingestion. Methionine supplementation significantly elevates hepatic GSH level and GSH/GSSG ratio, and lowered hepatic GSSG level as well as erythrocyte GSH level and GSH/GSSG ratio. In terms of activities of hepatic GSH related enzymes, γ-Glutamylcysteine synthetase activity increased with elevated dietary methionine supplementation. The hepatic glutathione reductase activity increased by long term high Se ingestion without supplementing methionine. Dietary methionine supplement decreased glutathione reductase activity. Long term high Se consumption ignificantly elevated glutathione-S-transferase activity, which was reduced by dietary methionine supplement. Although experimental diets of this study offered 23.2 mg/kg diet vitamin B2, consumption of 5 mg Se/kg diet which no added methionine for 12 weeks still elevated erythrocyte glutathione reductase activity coefficient, probably to the stage of marginal vitamin B2 deficiency. In summary, long term consumption of high Se diet caused growth retardation and hair loss, altered hepatic GSH metabolism and probably raised vitamin B2 requirement of rats. Dietary methionine supplementation may assist in relieving Se toxicity probably increasing GSH supply.