Maternal vitamin B12 deficiency in rats alters DNA methylation in metabolically important genes in their offspring

Tanwar, Vinay Singh; Ghosh, Sourav; Sati, Satish; Ghose, Subhoshree; Kaur, Lovejeet; Kumar, Kalle Anand; Shamsudheen, K. V.; Patowary, Ashok; Singh, Meghna; Jyothi, Vuskamalla; Kommineni, Pujitha; Sivasubbu, Sridhar; Scaria, Vinod; Raghunath, Manchala; Mishra, Rakesh; Chandak, Giriraj Ratan; Sengupta, Shantanu

doi:10.1007/s11010-020-03713-x

Cited by 20 publications

(11 citation statements)

References 52 publications

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“…Therefore, in the current era of omics, epigenome-wide association studies (EWAS) may help to fill the gap between large-scale genomic information and related applications ( Michels et al, 2013 ; Lee et al, 2014 ). Studies have shown that DNA methylation can lead to phenotypic changes in feeding and environmental conditions, resulting in productivity changes and animal disease risk ( Boddicker et al, 2016 ; Tao et al, 2019 ; Tanwar et al, 2020 ). For example, a comparison of DNA methylation distribution between fast and slow growing broilers found that a total of 13,294 methylation genes were detected, of which 132 differentially methylated genes were related to growth and metabolism ( Hu et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep

Tian

Yang

et al. 2021

Front. Genet.

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Hair follicle growth and development are a complex and long-term physiological process, which is regulated by a variety of physical factors and signal pathways. Increasing the understanding of the epigenetic regulation and function of candidate genes related to hair follicle development will help to better understand the molecular regulatory mechanisms of hair follicle development. In this study, the methylated DNA immunoprecipitation sequencing (MeDIP-seq) was used to obtain the genome-wide methylation map of the hair follicular development of Super Merino sheep in six stages (fetal skin tissue at 65d, 85d, 105d, 135d, 7d, and 30d after birth). Combined with the results of previous RNA-sequencing, 65 genes were screened out that were both differential methylation and differential expression, including EDN1, LAMC2, NR1D1, RORB, MyOZ3, and WNT2 gene. Differential methylation genes were enriched in Wnt, TNF, TGF-beta, and other signaling pathways related to hair follicle development. The bisulfite sequencing PCR results and MeDIP-seq were basically consistent, indicating that the sequencing results were accurate. As a key gene in the Wnt signaling pathway, both differential methylation and expression gene identified by MeDIP-seq and RNA-seq, further exploration of the function of WNT2 gene revealed that the DNA methylation of exon 5 (CpG11 site) promoted the expression of WNT2 gene. The overexpression vector of lentivirus pLEX-MCS-WNT2 was constructed, and WNT2 gene effectively promoted the proliferation of sheep skin fibroblasts. The results showed that WNT2 gene could promote the growth and development of skin and hair follicles. The results of this study will provide a theoretical basis for further research on sheep hair follicle development and gene regulation mechanisms.

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Section: Discussionmentioning

confidence: 99%

Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep

Tian

Yang

et al. 2021

Front. Genet.

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“…Studies performed in rats subjected to a vitamin B 12 restricted diet showed elevation of triglycerides that was transmissible to the offspring [ 63 ]. Follow-up work revealed that vitamin B 12 deficiency altered DNA methylation in rats including genes involved in fatty acid metabolism [ 64 ]. The authors suggested that the association between vitamin B 12 status and triglycerides is causal, as rehabilitation of the vitamin B 12 -restricted animals with a diet rich in vitamin B 12 corrected the abnormal concentrations of triglycerides [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases

Hinkel

Schmitt

Wurm

et al. 2020

JCM

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Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.

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“…In another study, rehabilitation at weaning did not show any improvement in the onset of adverse outcomes, but rehabilitation at parturition did (173). In another rodent study, altered DNA methylation in metabolic-related genes in the offspring of maternal vitamin B12 restriction was reported, and rehabilitation at conception and parturition partly reversed the methylation status (174).…”

Section: Vitamin B12 and Folatementioning

confidence: 95%

The Effect and Potential Mechanism of Maternal Micronutrient Intake on Offspring Glucose Metabolism: An Emerging Field

Zhang

Xiao

2021

Front. Nutr.

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Diabetes has become the most common metabolic disease around the world. In addition to genetic and environmental factors in adulthood, the early life environment is critical to the progression of diabetes in adults, especially the environment during the fetal period; this concept is called “fetal programming.” Substantial evidence has illustrated the key role of early life macronutrient in programming metabolic diseases. Recently, the effect of maternal micronutrient intake on offspring glucose metabolism during later life has become an emerging field. This review focuses on updated human and animal evidence about the effect of maternal micronutrient status on offspring glucose metabolism and the underlying mechanism.

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Maternal vitamin B12 deficiency in rats alters DNA methylation in metabolically important genes in their offspring

Cited by 20 publications

References 52 publications

Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep

Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep

Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases

The Effect and Potential Mechanism of Maternal Micronutrient Intake on Offspring Glucose Metabolism: An Emerging Field

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