Acute exercise alters homocysteine plasma concentration in an intensity-dependent manner due increased methyl flux in liver of rats

Riberio, Diogo Farias; Cella, Paola S; Silva, Lilian Eslaine Costa Mendes da; Jordão, Alceu Afonso; Deminice, Rafael

doi:10.1016/j.lfs.2018.01.003

Cited by 9 publications

(10 citation statements)

References 29 publications

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“…The observed decrease in methionine and increase in tHcy post-exhaustive exercise may thus reflect increased transmethylation in which DNA, histones and other macromolecules are methylated in response to exercise. Indeed, one animal experiment showed that plasma methionine availability is an important determinant of intracellular methylation capacity (Mentch et al, 2015), and postexercise elevations in tHcy is thought to reflect increased methyl flux in tissues (Riberio et al, 2018). It has been reported that acute exercise induced immediate hypomethylation of several genes in skeletal muscle biopsies obtained from healthy individuals (Barres et al, 2012).…”

Section: Potential Mechanismsmentioning

confidence: 99%

“…Hypo-and hypertmethylation of DNA and histones are thought to be implicated in tissue response to acute and long-term exercise (Barres et al, 2012;Voisin et al, 2015;Seaborne et al, 2018;Hunter et al, 2019;Landen et al, 2019;Turner et al, 2019), and are dependent on availability of plasma and cellular methionine concentrations (Mentch et al, 2015). Tissue consumption of methionine for methylation reactions have been demonstrated in exercising mice (Riberio et al, 2018) and has been linked to observed post-exercise increases in plasma total homocysteine (tHcy) in humans (Deminice et al, 2016). In addition to being a potential marker of methylation reactions, elevated tHcy may impair endothelial nitric oxide synthesis (Stühlinger et al, 2001) with potential adverse effects on recovery and performance (Kingwell, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Exhaustive Exercise and Post-exercise Protein Plus Carbohydrate Supplementation Affect Plasma and Urine Concentrations of Sulfur Amino Acids, the Ratio of Methionine to Homocysteine and Glutathione in Elite Male Cyclists

et al. 2020

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Plasma and tissue sulfur amino acid (SAA) availability are crucial for intracellular methylation reactions and cellular antioxidant defense, which are important processes during exercise and in recovery. In this randomized, controlled crossover trial among eight elite male cyclists, we explored the effect of exhaustive exercise and post-exercise supplementation with carbohydrates and protein (CHO+PROT) vs. carbohydrates (CHO) on plasma and urine SAAs, a potential new marker of methylation capacity (methionine/total homocysteine ratio [Met/tHcy]) and related metabolites. The purpose of the study was to further explore the role of SAAs in exercise and recovery. Athletes cycled to exhaustion and consumed supplements immediately after and in 30 min intervals for 120 min post-exercise. After ~18 h recovery, performance was tested in a time trial in which the CHO+PROT group cycled 8.5% faster compared to the CHO group (41:53 ± 1:51 vs. 45:26 ± 1:32 min, p < 0.05). Plasma methionine decreased by ~23% during exhaustive exercise. Two h post-exercise, further decline in methionine had occured by ~55% in the CHO group vs. ~33% in the CHO+PROT group (pgroup × time < 0.001). The Met/tHcy ratio decreased by ~33% during exhaustive exercise, and by ~54% in the CHO group vs. ~27% in the CHO+PROT group (pgroup × time < 0.001) post-exercise. Plasma cystathionine increased by ~72% in the CHO group and ~282% in the CHO+PROT group post-exercise (pgroup × time < 0.001). Plasma total cysteine, taurine and total glutathione increased by 12% (p = 0.03), 85% (p < 0.001) and 17% (p = 0.02), respectively during exhaustive exercise. Using publicly available transcriptomic data, we report upregulated transcript levels of skeletal muscle SLC7A5 (log2 fold-change: 0.45, FDR:1.8e−07) and MAT2A (log2 fold-change: 0.38, FDR: 3.4e−0.7) after acute exercise. Our results show that exercise acutely lowers plasma methionine and the Met/tHcy ratio. This response was attenuated in the CHO+PROT compared to the CHO group in the early recovery phase potentially affecting methylation capacity and contributing to improved recovery.

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Section: Potential Mechanismsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exhaustive Exercise and Post-exercise Protein Plus Carbohydrate Supplementation Affect Plasma and Urine Concentrations of Sulfur Amino Acids, the Ratio of Methionine to Homocysteine and Glutathione in Elite Male Cyclists

et al. 2020

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“…Dysfunction of liver alters methionine metabolism, resulting in elevated homocysteine that is released into the plasma. In return, homocysteine can in uence the status of liver as well (16). Our previous study proposed that ER stress might explain the pathogenic effects of homocysteine on liver injury, while its molecular mechanism remains obscure (17).…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of miR-212-5p Facilitates Homocysteine-Induced Hepatocytes Apoptosis Via Targeting PSMD10

Zhang¹,

Xiao²,

Ma³

et al. 2020

Preprint

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Background: Increasing evidences supported that elevated homocysteine (Hcy) levels contribute to cell apoptosis is implicated in the pathogenesis of liver injury, it correlates with liver disease severity. However, the underlying mechanism of apoptosis in Hcy-mediated liver injury remains obscure. Results: In this study, we found that homocysteine increases ER stress-mediated apoptosis and aggravates liver injury through up-regulation of PSMD10 expression in cbs+/- mice mice fed with high methionine diet and hepatocytes treated with homocysteine in vitro. Knockdown of PSMD10 expression remarkably reduced ER stress or apoptosis-associated protein in hepatocytes exposed to homocysteine. Moreover, bioinformatics analysis revealed that PSMD10 is a potential target gene of miR-212-5p, and luciferase reporter assay also confirmed that miR-212-5p negatively regulated PSMD10 expression by direct binding to its 3’-UTR regions. Subsequently, over-expression of miR-212-5p inhibited ER stress-mediated hepatocytes apoptosis though targeting PSMD10, all of which were abrogated by knockdown of miR-212-5p expression. Further study showed that the interaction between PSMD10 and GRP78 accelerated ER stress-mediated hepatic apoptosis induced by homocysteine. Conclusion: Taken together, these results demonstrated that down-regulation of miR-212-5p facilitates homocysteine-induced hepatocytes apoptosis via targeting PSMD10, which provides novel insight into the mechanism of homocysteine induced apoptosis in liver injury.

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“…Interestingly, compared to control, moderate exercise was much more e cient on decreasing DMGV than vigorous exercise with an equal effect on IHTG reduction, though vigorous exercise was more e cient on improvement of weight, waist circumference, body fat and visceral fat. It was con rmed that various exercise intensities impacted plasma metabolic pro le differently [18][19][20] , and low-intensity exercise favors a fat oxidation rate than in the high intensity exercise group with a greater decrease in body mass and fat mass 21 , thus, we considered that moderate exercise bene ts DMGV metabolism better than vigorous exercise might due to the better improvement on enzyme related to DMGV metabolism and oxidation ability, which needed further investigation.…”

Section: Discussionmentioning

confidence: 99%

Dimethylguanidino valeric acid is independently associated with intrahepatic triglyceride content in patients with nonalcoholic fatty liver disease (NAFLD) and decreased after long-term exercise

Huang²,

Huang

et al. 2020

Preprint

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Backgrounds: Dimethylguanidino valeric acid (DMGV) is closely associated with nonalcoholic fatty liver disease (NAFLD), the most recommended therapy of NAFLD is Exercise. Our aim was to investigate the correlation between DMGV concentrations and clinical characters in patients with NAFLD, and assessed the effect on DMGV concentrations changes after 6 month exercise training.Methods: NAFLD individuals (n = 220) were selected and randomly divided into control group (n = 74), moderate exercise group (n = 73) and vigorous exercise group (n = 73) with 6 month followed-up. Clinical characteristics were obtained from our previous clinical trial, serum DMGV levels were determined by a validated ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method.Results: On baseline, DMGV levels were positive associated with age, visceral fat and intrahepatic triglyceride (IHTG) content, and inversely associated with fasting blood glucose and diastolic blood pressure. In addition, the association between DMGV levels and IHTG content remained significant after adjusting other main clinical characters (β coefficient = 0.174, P = 0.018). After 6 month exercise training, IHTG was decreased by both exercise intensities without a significant difference (P = 0.45), however, moderate exercise was more efficient on DMGV decreasing than vigorous exercise (-9.96 to 2.27 ng/ml, P < 0.001 for moderate exercise; -4.53 to 4.56 ng/ml, P = 0.762 for vigorous exercise) with a significant difference (P = 0.047).Conclusions: DMGV was a potential indicator during development and progression of NAFLD, and moderate exercise was more efficient on metabolic changes than vigorous exercise with equal IHTG improvement, suggesting a priority of exercise intensity during NAFLD treatment.ClinicalTrials.gov Identifier: NCT01418027, August 16, 2011

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Acute exercise alters homocysteine plasma concentration in an intensity-dependent manner due increased methyl flux in liver of rats

Abstract: Our data provided evidence that acute exercise increases plasma Hcy concentration due to the augmented requirement for methylated compounds that increases liver SAM consumption. Also, Hcy remethylation and transsulfuration are coordinately regulated to maintain methyl balance.

Cited by 9 publications

References 29 publications

Exhaustive Exercise and Post-exercise Protein Plus Carbohydrate Supplementation Affect Plasma and Urine Concentrations of Sulfur Amino Acids, the Ratio of Methionine to Homocysteine and Glutathione in Elite Male Cyclists

Exhaustive Exercise and Post-exercise Protein Plus Carbohydrate Supplementation Affect Plasma and Urine Concentrations of Sulfur Amino Acids, the Ratio of Methionine to Homocysteine and Glutathione in Elite Male Cyclists

Down-Regulation of miR-212-5p Facilitates Homocysteine-Induced Hepatocytes Apoptosis Via Targeting PSMD10

Dimethylguanidino valeric acid is independently associated with intrahepatic triglyceride content in patients with nonalcoholic fatty liver disease (NAFLD) and decreased after long-term exercise

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