scholarly journals Unique adaptations in neonatal hepatic transcriptome, nutrient signaling, and one-carbon metabolism in response to feeding ethyl cellulose rumen-protected methionine during late-gestation in Holstein cows

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Valentino Palombo ◽  
Abdulrahman Alharthi ◽  
Fernanda Batistel ◽  
Claudia Parys ◽  
Jessie Guyader ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Responses ◽  
Carbon Metabolism ◽  
Ethyl Cellulose ◽  
In Utero ◽  
Holstein Cows ◽  
Nutrient Metabolism ◽  
Transsulfuration Pathway ◽  
One Carbon Metabolism ◽  
Hepatic Transcriptome

Abstract Background Methionine (Met) supply during late-pregnancy enhances fetal development in utero and leads to greater rates of growth during the neonatal period. Due to its central role in coordinating nutrient and one-carbon metabolism along with immune responses of the newborn, the liver could be a key target of the programming effects induced by dietary methyl donors such as Met. To address this hypothesis, liver biopsies from 4-day old calves (n = 6/group) born to Holstein cows fed a control or the control plus ethyl-cellulose rumen-protected Met for the last 28 days prepartum were used for DNA methylation, transcriptome, metabolome, proteome, and one-carbon metabolism enzyme activities. Results Although greater withers and hip height at birth in Met calves indicated better development in utero, there were no differences in plasma systemic physiological indicators. RNA-seq along with bioinformatics and transcription factor regulator analyses revealed broad alterations in ‘Glucose metabolism’, ‘Lipid metabolism, ‘Glutathione’, and ‘Immune System’ metabolism due to enhanced maternal Met supply. Greater insulin sensitivity assessed via proteomics, and efficiency of transsulfuration pathway activity suggested beneficial effects on nutrient metabolism and metabolic-related stress. Maternal Met supply contributed to greater phosphatidylcholine synthesis in calf liver, with a role in very low density lipoprotein secretion as a mechanism to balance metabolic fates of fatty acids arising from the diet or adipose-depot lipolysis. Despite a lack of effect on hepatic amino acid (AA) transport, a reduction in metabolism of essential AA within the liver indicated an AA ‘sparing effect’ induced by maternal Met. Conclusions Despite greater global DNA methylation, maternal Met supply resulted in distinct alterations of hepatic transcriptome, proteome, and metabolome profiles after birth. Data underscored an effect on maintenance of calf hepatic Met homeostasis, glutathione, phosphatidylcholine and taurine synthesis along with greater efficiency of nutrient metabolism and immune responses. Transcription regulators such as FOXO1, PPARG, E2F1, and CREB1 appeared central in the coordination of effects induced by maternal Met. Overall, maternal Met supply induced better immunometabolic status of the newborn liver, conferring the calf a physiologic advantage during a period of metabolic stress and suboptimal immunocompetence.

scholarly journals Parental Selenium Nutrition Affects the One-Carbon Metabolism and the Hepatic DNA Methylation Pattern of Rainbow Trout (Oncorhynchus mykiss) in the Progeny

Life ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 121 ◽  
Author(s):  
Pauline Wischhusen ◽  
Takaya Saito ◽  
Cécile Heraud ◽  
Sadasivam J. Kaushik ◽  
Benoit Fauconneau ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rainbow Trout ◽  
Carbon Metabolism ◽  
Methylation Pattern ◽  
Mrna Levels ◽  
Transsulfuration Pathway ◽  
Methionine Cycle ◽  
Dna Methylation Pattern ◽  
One Carbon Metabolism ◽  
The One

Selenium is an essential micronutrient and its metabolism is closely linked to the methionine cycle and transsulfuration pathway. The present study evaluated the effect of two different selenium supplements in the diet of rainbow trout (Onchorhynchus mykiss) broodstock on the one-carbon metabolism and the hepatic DNA methylation pattern in the progeny. Offspring of three parental groups of rainbow trout, fed either a control diet (NC, basal Se level: 0.3 mg/kg) or a diet supplemented with sodium selenite (SS, 0.8 mg Se/kg) or hydroxy-selenomethionine (SO, 0.7 mg Se/kg), were collected at swim-up fry stage. Our findings suggest that parental selenium nutrition impacted the methionine cycle with lower free methionine and S-adenosylmethionine (SAM) and higher methionine synthase (mtr) mRNA levels in both selenium-supplemented treatments. DNA methylation profiling by reduced representation bisulfite sequencing (RRBS) identified differentially methylated cytosines (DMCs) in offspring livers. These DMCs were related to 6535 differentially methylated genes in SS:NC, 6890 in SO:NC and 7428 in SO:SS, respectively. Genes with the highest methylation difference relate, among others, to the neuronal or signal transmitting and immune system which represent potential targets for future studies.

scholarly journals In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

BMC Medicine ◽  
2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Amanda J Drake ◽  
Peter J O’Shaughnessy ◽  
Siladitya Bhattacharya ◽  
Ana Monteiro ◽  
David Kerrigan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Carbon Metabolism ◽  
Fetal Liver ◽  
In Utero ◽  
In Utero Exposure ◽  
Human Fetal Liver ◽  
One Carbon Metabolism

Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism

Oncogene ◽  
2017 ◽  
Vol 37 (7) ◽  
pp. 963-970 ◽  
Author(s):  
E Cuyàs ◽  
S Fernández-Arroyo ◽  
S Verdura ◽  
R Á-F García ◽  
J Stursa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Carbon Metabolism ◽  
Global Dna Methylation ◽  
One Carbon Metabolism

scholarly journals Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

2018 ◽  
Vol 19 (10) ◽  
pp. 3106 ◽  
Author(s):  
Kuniyasu Soda
Keyword(s):  
Dna Methylation ◽  
Carbon Metabolism ◽  
Methylation Status ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Dna Methyltransferases ◽  
Polyamine Metabolism ◽  
Methyl Group ◽  
Wide Range ◽  
One Carbon Metabolism

Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.

scholarly journals Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Anna K. Knight ◽  
Hea Jin Park ◽  
Dorothy B. Hausman ◽  
Jennifer M. Fleming ◽  
Victoria L. Bland ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Carbon Metabolism ◽  
Methylation Status ◽  
One Carbon Metabolism

scholarly journals Allosteric inhibition of MTHFR prevents futile SAM cycling and maintains nucleotide pools in one-carbon metabolism

2020 ◽  
Vol 295 (47) ◽  
pp. 16037-16057 ◽  
Author(s):  
Muskan Bhatia ◽  
Jyotika Thakur ◽  
Shradha Suyal ◽  
Ruchika Oniel ◽  
Rahul Chakraborty ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Methylenetetrahydrofolate Reductase ◽  
Isotope Labeling ◽  
Redox Homeostasis ◽  
Regulatory Region ◽  
Regulatory Control ◽  
Growth Defect ◽  
Transsulfuration Pathway ◽  
One Carbon Metabolism ◽  
The Impact

Methylenetetrahydrofolate reductase (MTHFR) links the folate cycle to the methionine cycle in one-carbon metabolism. The enzyme is known to be allosterically inhibited by SAM for decades, but the importance of this regulatory control to one-carbon metabolism has never been adequately understood. To shed light on this issue, we exchanged selected amino acid residues in a highly conserved stretch within the regulatory region of yeast MTHFR to create a series of feedback-insensitive, deregulated mutants. These were exploited to investigate the impact of defective allosteric regulation on one-carbon metabolism. We observed a strong growth defect in the presence of methionine. Biochemical and metabolite analysis revealed that both the folate and methionine cycles were affected in these mutants, as was the transsulfuration pathway, leading also to a disruption in redox homeostasis. The major consequences, however, appeared to be in the depletion of nucleotides. 13C isotope labeling and metabolic studies revealed that the deregulated MTHFR cells undergo continuous transmethylation of homocysteine by methyltetrahydrofolate (CH3THF) to form methionine. This reaction also drives SAM formation and further depletes ATP reserves. SAM was then cycled back to methionine, leading to futile cycles of SAM synthesis and recycling and explaining the necessity for MTHFR to be regulated by SAM. The study has yielded valuable new insights into the regulation of one-carbon metabolism, and the mutants appear as powerful new tools to further dissect out the intersection of one-carbon metabolism with various pathways both in yeasts and in humans.

Modeling folate, one-carbon metabolism, and DNA methylation

2008 ◽  
Vol 66 ◽  
pp. S27-S30 ◽  
Author(s):  
Cornelia M Ulrich ◽  
Michael C Reed ◽  
H Frederik Nijhout
Keyword(s):  
Dna Methylation ◽  
Carbon Metabolism ◽  
One Carbon Metabolism

scholarly journals Genetic polymorphisms relevant for one-carbon metabolism show no effect on homocysteine plasma levels and DNA methylation in alcoholism

2009 ◽  
Vol 19 (4) ◽  
pp. 215-216 ◽  
Author(s):  
Bernd Lenz ◽  
Carmen Soehngen ◽  
Michael Linnebank ◽  
Annemarie Heberlein ◽  
Helge Frieling ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Polymorphisms ◽  
Carbon Metabolism ◽  
Plasma Levels ◽  
One Carbon Metabolism

scholarly journals Study on the Relationship Between Folate, Dna Methylation and Esophagus Cancer

2017 ◽  
Vol 1 (3) ◽  
Author(s):  
Huang Guiling
Keyword(s):  
Dna Methylation ◽  
Carbon Metabolism ◽  
Early Screening ◽  
Methyl Group ◽  
Esophagus Cancer ◽  
Multiple Factors ◽  
Chinese Characteristic ◽  
The World ◽  
One Carbon Metabolism ◽  
The Relationship

Esophagus cancer is a common malignant tumor in China, and itsprevalence rate and fatality rate are the highest in the world whoseoccurrence is related to multiple factors, including family heredity,race, gender, region, diet and so on. Esophagus cancer is the diseasewith the most Chinese characteristic. The pathogenesis of esophagus cancer is very complicated, and the epigenetics in the pathogenetic process has become the current research hotspot, and the reversible feature provides a new direction for the early screening, prevention and treatment of esophagus cancer. DNA methylation is the most deep epigenetics in the current study, and the pattern of genome methylation is often abnormal in the cancerization of esophagus cancer. The folate, as the methyl group donor, and B-vitamins related to one-carbon metabolism, shall directly influence the condition of DNA methylation, give rise to the change of epigenetics, affect the occurrence of esophagus cancer. This paper summarizes the relationship among the occurrence of esophagus cancer and folate, several kinds of B-vitamins related to one-carbon metabolism, DNA methylation.

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