scholarly journals Steatosis in Mice Is Associated with Gender, Folate Intake, and Expression of Genes of One-Carbon Metabolism

2010 ◽  
Vol 140 (10) ◽  
pp. 1736-1741 ◽  
Author(s):  
Karen E. Christensen ◽  
Qing Wu ◽  
Xiaoling Wang ◽  
Liyuan Deng ◽  
Marie A. Caudill ◽  
...  
2008 ◽  
Vol 99 (2) ◽  
pp. 379-389 ◽  
Author(s):  
Linda Sharp ◽  
Julian Little ◽  
Nigel T. Brockton ◽  
Seonaidh C. Cotton ◽  
Lindsey F. Masson ◽  
...  

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case–control study of folate intake, related dietary factors andMTHFRpolymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CTv.CC = 0·77 (95 % CI 0·52, 1·16); OR for TTv.CC = 0·62 (95 % CI 0·31, 1·24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0·81 (95 % CI 0·45, 1·49)). There were significant interactions between total folate and C677T (P = 0·029) and A1298C (P = 0·025), and total vitamin B6and both polymorphisms (C677T,P = 0·016; A1298C,P = 0·033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.


2012 ◽  
Vol 109 (6) ◽  
pp. 984-989 ◽  
Author(s):  
Marcella Martinelli ◽  
Luca Scapoli ◽  
Gabriella Mattei ◽  
Giampaolo Ugolini ◽  
Isacco Montroni ◽  
...  

The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case–control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G (rs1801198) and c.1026-394T>G (rs7286680). Considering the crucial biological function played by one-carbon metabolism genes, further investigations with larger cohorts of CRC patients are needed in order to confirm our preliminary results. These preliminary results indicate that TCN2 polymorphisms can be a susceptibility factor for CRC.


Author(s):  
Sang-Woon Choi ◽  
Simonetta Friso

AbstractInadequate folate intake and aging are each strongly implicated as important risk factors for certain cancers. Since both folate depletion and aging are strongly associated with hyperhomocysteinemia, genomic DNA hypomethylation, and increased uracil misincorporation into DNA, it appears that each of them enhances carcinogenesis by inducing a derangement of one-carbon metabolism that supplies one-carbons to biological methylation reactions and nucleotide synthesis. Recent studies have demonstrated that inadequate dietary folate and aging may interact and synergistically disturb the normal homeostasis of one-carbon metabolism, thereby provoking subsequent biochemical and molecular aberrations, including alterations in critical gene expression related to carcinogenesis. These studies have further indicated that modest folate supplementation may reverse or partially ameliorate those adverse effects induced by folate depletion and aging.


2020 ◽  
Vol 90 (1-2) ◽  
pp. 131-140 ◽  
Author(s):  
Mahshid Hatami ◽  
Farhad Vahid ◽  
Mohammad Esmaeil Akbari ◽  
Mahya Sadeghi ◽  
Fatemeh Ameri ◽  
...  

Abstract. Background: Some micronutrients like folate, vitamin B12, B6, and B2 are the source of coenzymes, which participate in one-carbon metabolism. Any disruption in this metabolism can interfere with DNA replication, repair and regulation of gene expression and ultimately promote the likelihood of carcinogenesis. This study aimed at investigating the relationship between the intakes of micronutrients involved in one-carbon metabolism with breast cancer (BrCa) and its subtype’s odds. Methods: Nutrients’ intake from diet and supplements were collected through interviewing 151 cases and 154 controls by a 168-item semiquantitative food frequency questionnaire. Logistic regression was used to determine the relationship between dietary and/or total intake of studied nutrients and odds of BrCa and its subtypes. Results: After adjusting the effects of confounding variables in the models, the odds of BrCa was significantly lower in the highest intake quartile compared with the lowest quartile for total intake of vitamin B2 (OR = 0.17, 95% CI, 0.07–0.39; Ptrend < 0.001), vitamin B6 (OR = 0.11, 95% CI, 0.05–0.27; Ptrend < 0.001), vitamin B12 (OR = 0.20, 95% CI, 0.09–0.43; Ptrend < 0.001) and folate (OR = 0.09, 95% CI, 0.04–0.21; Ptrend < 0.001). Also, those with the highest quartile of vitamin B6, B12, B2 and folate intake compared with the lowest quartile were less likely to develop estrogen receptor (ER)+ and progesterone receptor (PR)+ subtypes, ER- status, PR- and human epidermal growth factor receptor 2 (HER2)+ subtypes and HER2- status. Conclusion: High intakes of vitamins B2, B6 and folate are associated with reduced odds of BrCa in overall and all ER, PR and HER2 subtypes. Also, high intakes of vitamin B12 reduced the odds of all subtypes of BrCa except ER- subtype.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 126-126
Author(s):  
Christopher Choi ◽  
Scott Leiser ◽  
Charles Evans ◽  
Daniel Beard

Abstract Nematode flavin-containing monooxygenase-2 (fmo-2) is induced by dietary restriction and hypoxia, and is required for the longevity and health benefits of these pathways. It is also sufficient to confer these benefits when overexpressed. As FMOs are well-conserved across taxa, the fmo-2 mechanism has high translational potential. To determine the changes that occur following fmo-2 induction, we performed RNA-seq and untargeted metabolomics analyses. Our data reveal that one-carbon metabolism (OCM) is significantly altered by fmo-2 overexpression. OCM is a nexus for essential metabolic pathways, including transmethylation, transsulfuration, nucleotide synthesis, and amino acid metabolism. We hypothesized that fmo-2 confers longevity benefits by altering key metabolic processes within or downstream of OCM. To test this, we asked whether fmo-2 and OCM interact to regulate longevity by knocking down expression of genes involved with OCM and measuring lifespan and oxidative stress resistance. To understand the biological implications of these interactions, we generated a computational model using qPCR data of key OCM-related genes to predict changes in OCM metabolic flux. Our model predicts significant changes in OCM flux that are regulated by fmo-2 expression levels and are consistent with our RNAi and multi-omics results. We are now testing this model by knocking down genes downstream of OCM to determine their role in fmo-2-mediated benefits. Preliminary results support our hypothesis that changes in metabolic flux through OCM are involved downstream of fmo-2 expression, and may also implicate the UPRER in this pathway. Our future work will elucidate this mechanism and link stress perception and fmo-2-mediated longevity.


2015 ◽  
Vol 115 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Fang-fang Zeng ◽  
Yuan-ting Liu ◽  
Xiao-ling Lin ◽  
Yu-ying Fan ◽  
Xing-lan Zhang ◽  
...  

AbstractMany studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2–4 (v. 1) were 0·66 (95 % CI 0·48, 0·91), 0·52 (95 % CI 0·37, 0·74) and 0·34 (95 % CI 0·23, 0·50) (Ptrend<0·001) for folate and 0·72 (95 % CI 0·52, 1·00), 0·55 (95 % CI 0·39, 0·78) and 0·44 (95 % CI 0·30, 0·63) (Ptrend<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (Pinteraction=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ting Chen ◽  
Na Tao ◽  
Sheng Yang ◽  
Dafang Cao ◽  
Xun Zhao ◽  
...  

Objective: This study aimed to investigate the associations between dietary one-carbon metabolism-related nutrients (betaine, choline, methionine, folate, vitamin B6, and vitamin B12) and fluorosis among the Chinese population in an area known for coal-burning fluorosis.Methods: A cross-sectional study was conducted, with 653 fluorosis patients and 241 non-fluorosis participants. Dietary intake was acquired using a validated semi-quantitative 75-item food frequency questionnaire. The risk associations were assessed by unconditional logistical regression.Results: We observed a significant inverse association between dietary betaine, total choline, methionine, folate, vitamin B6, and choline species and fluorosis. The adjusted OR (95% CI) in the highest quartile of consumption compared with the lowest were 0.59 (0.37–0.94) (P-trend = 0.010) for betaine intake, 0.45 (0.28–0.73) (P-trend = 0.001) for total choline intake, 0.45 (0.28–0.72) (P-trend &lt; 0.001) for methionine intake, 0.39 (0.24–0.63) (P-trend &lt; 0.001) for folate intake, 0.38 (0.24–0.62) (P-trend &lt; 0.001) for vitamin B6 intake, and 0.46 (0.28–0.75) (P-trend = 0.001) for total choline plus betaine intake. Dietary intakes of choline-containing compounds, phosphatidylcholine, free choline, glycerophosphocholine, and phosphocholine were also inversely associated with lower fluorosis (all P-trend &lt; 0.05). No significant associations were observed between dietary vitamin B12 or sphingomyelin and fluorosis.Conclusion: The present study suggested that the higher dietary intakes of specific one-carbon metabolism-related nutrients, such as betaine, choline, methionine, folate, and vitamin B6, are associated with lower fluorosis prevalence.


2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.


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