Sulfur amino acid metabolism in Zucker diabetic fatty rats

Kwak, Hui Chan; Kim, Youngmi; Oh, Soo Jin; Kim, Sang Kyum

doi:10.1016/j.bcp.2015.05.014

Cited by 18 publications

(17 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increase in the level of methionine in the liver of obese rats was also reported by Serkova et al [28]. This higher level of methionine could resonate and be a part of general and complicated trends of imbalance in amino acids metabolism in the livers of obese rats [29]. We were interested in investigating the effects of obesity on methionine content in the liver because almost half of human or animal body methionine metabolism happens in the liver [30] and methionine participates in biological methylation reactions and glutathione synthesis.…”

Section: Discussionsupporting

confidence: 54%

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models

et al. 2017

View full text Add to dashboard Cite

The prevalence of the overweight and obesity is on the rise worldwide. Obesity can increase the risk of certain cancers and liver steatosis development. Previously, we reported that obesity increased liver steatosis in a mammary tumor model, but little is known about the effects of obesity in the liver in regard to global DNA methylation, DNA damage, and oxidative/nitrosative stress. Using a mammary tumor model, we investigated the effects of obesity on oxidative stress and DNA reaction. Five-week-old lean and obese female rats were used. At 50 days of age, all rats received 7,12-dimethylbenz(α)anthracene (DMBA) and were sacrificed 155 days later. HPLC with electrochemical and ultraviolet detection and LC-MS were used. Obesity caused higher (p < 0.0004) methionine levels, had no effect (p < 0.055) on SAM levels, caused lower (p < 0.0005) SAH levels, caused higher (p < 0.0005) SAM/SAH ratios, and increased (p < 0.02) global DNA methylation. Levels of free reduced GSH were not significantly lower (p < 0.08), but free oxidized GSSG was higher (p < 0.002) in obese rats. The GSH/GSSG ratio was lower (p < 0.0001), and oxidized guanosine was higher (p < 0.002) in DNA of obese rats compared to lean rats. Obesity caused significant oxidative/nitrosative stress, oxidative DNA damage, and change of DNA methylation pattern in the liver, and these changes may contribute to the development of liver steatosis in breast cancer models.

show abstract

Section: Discussionsupporting

confidence: 54%

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A new mathematical MMC model was successfully developed using plasma measurements of both methionine and homocysteine, and was characterized using seven compartments. From the prior study [ 14 ], we found that the plasma concentration kinetics of methionine were similar in the ZDF and control groups, while homocysteine exhibited a different kinetic pattern. Furthermore, since the hepatic concentrations of SAM and SAH did not differ between control and ZDF rats, the K CM , K MC , K MS , K SS , K EL , and V c parameters were predicted without consideration of disease status.…”

Section: Resultsmentioning

confidence: 91%

“…Blood samples were collected at 0, 10, 30, 60, 120, 210, 300, and 420 min after administration. Methionine and homocysteine concentrations were determined using LC-ESI/MS/MS; the details of the study design were described earlier [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, some studies reported that the levels of homocysteine were either reduced or normal under diabetic conditions [ 11 , 12 ]. These inconsistent results seem to be attributable to varying extents of hepatic and renal dysfunction [ 11 , 13 ], the methionine content of the diet [ 14 , 15 ], and the clinical status of diabetic disease [ 12 , 16 , 17 ]. Here, we focused on the fact that a high-fat diet affects the metabolism of both methionine and homocysteine in a diabetic rat model [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…These inconsistent results seem to be attributable to varying extents of hepatic and renal dysfunction [ 11 , 13 ], the methionine content of the diet [ 14 , 15 ], and the clinical status of diabetic disease [ 12 , 16 , 17 ]. Here, we focused on the fact that a high-fat diet affects the metabolism of both methionine and homocysteine in a diabetic rat model [ 14 ]. Thus, 0we hypothesized that long-term administration of a high-methionine diet to T2DM rats with normal renal function may create metabolic changes, culminating in an elevated level of circulating homocysteine.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF) rats as a T2DM animal model after consumption of a Methionine-rich diet

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundAlthough alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model.MethodThe model building and simulation were performed using NONMEM® (ver. 7.3.0) assisted by Perl-Speaks-NONMEM (PsN, ver. 4.3.0). Model parameters were derived using first-order conditional estimation method with interactions permitted among the parameters (FOCE-INTER). NCA was conducted using Phoenix (ver. 6.4.0). For all tests, we considered a P-value < 0.05 to reflect statistical significance.ResultsOur model featured seven compartments that considered all parts of the cycle by applying non-linear mixed effects model. Conversion of S-adenosyl-L-homocysteine (SAH) to homocysteine increased and the metabolism of homocysteine was reduced under diabetic conditions, and consequently homocysteine accumulated in the elimination phase.Using our model, we performed simulations to compare the changes in plasma methionine and homocysteine concentrations between ZDF and normal rats, by multiple administrations of the methionine-rich diet of 1 mmol/kg, daily for 60 days. The levels of methionine and homocysteine were elevated approximately two- and three-fold, respectively, in ZDF rats, while there were no changes observed in the normal control rats.ConclusionThese results can be interpreted to mean that both methionine and homocysteine will accumulate in patients with T2DM, who regularly consume high-methionine foods.

show abstract

Dietary Supplementation of Methyl Donor l‐Methionine Alters Epigenetic Modification in Type 2 Diabetes

Navik

Sheth

Kabeer

et al. 2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope The aim of the current study is to evaluate whether l‐methionine supplementation (l‐Met‐S) improves type 2 diabetes‐induced alterations in glucose and lipid metabolism by modulating one‐carbon metabolism and methylation status. Methods and Results Diabetes is induced in male Sprague–Dawley rats using high‐fat diet and low dose streptozotocin. At the end of study, various biochemical parameters, immunoblotting, qRT‐PCR and ChIP‐qPCR are performed. The first evidence that l‐Met‐S activates p‐AMPK and SIRT1, very similar to “metformin,” is provided. l‐Met‐S improves the altered key one‐carbon metabolites in diabetic rats by modulating methionine adenosyl transferase 1A and cystathione β synthase expression. qRT‐PCR shows that l‐Met‐S alleviates diabetes‐induced increase in Forkhead transcription factor 1 expression and thereby regulating genes involved in glucose (G6pc, Pdk4, Pklr) and lipid metabolism (Fasn). Interestingly, l‐Met‐S inhibits the increased expression of DNMT1 and also prevents methylation of histone H3K36me2 under diabetic condition. ChIP assay shows that persistent increase in abundance of histone H3K36me2 on the promoter region of FOXO1 in diabetic rats and it is recovered by l‐Met‐S. Conclusion The first evidence that dietary supplementation of l‐Met prevents diabetes‐induced epigenetic alterations and regulating methionine levels can be therapeutically exploited for the treatment of metabolic diseases is provided.

show abstract

Sulfur amino acid metabolism in Zucker diabetic fatty rats

Cited by 18 publications

References 48 publications

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models

Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF) rats as a T2DM animal model after consumption of a Methionine-rich diet

Dietary Supplementation of Methyl Donor l‐Methionine Alters Epigenetic Modification in Type 2 Diabetes

Contact Info

Product

Resources

About