Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice

Li, Wei; Tang, Renqiao; Ma, Feifei; Ouyang, Shengrong; Liu, Zhuo; Wu, Jianxin

doi:10.1016/j.jnutbio.2018.05.010

Cited by 47 publications

(35 citation statements)

References 48 publications

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“…While ADCY3 has no clearly defined role in skeletal muscle, it catalyzes the formation of the signalling molecule cAMP in response to G-protein signalling 44 , and regulates Ca 2+ -dependent insulin secretion. Its methylation has been demonstrated to change in adipose tissue in response to altered nutrition 45 , but no methylation data currently exists in skeletal muscle, other than that identified in the present manuscript.…”

Section: Discussionmentioning

confidence: 67%

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Turner

Seaborne

Sharples

2019

Sci Rep

143

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Transcriptome wide changes in human skeletal muscle after acute (anabolic) and chronic resistance exercise (RE) induced hypertrophy have been extensively determined in the literature. We have also recently undertaken DNA methylome analysis (850,000 + CpG sites) in human skeletal muscle after acute and chronic RE, detraining and retraining, where we identified an association between DNA methylation and epigenetic memory of exercise induced skeletal muscle hypertrophy. However, it is currently unknown as to whether all the genes identified in the transcriptome studies to date are also epigenetically regulated at the DNA level after acute, chronic or repeated RE exposure. We therefore aimed to undertake large scale bioinformatical analysis by pooling the publicly available transcriptome data after acute (110 samples) and chronic RE (181 samples) and comparing these large data sets with our genome-wide DNA methylation analysis in human skeletal muscle after acute and chronic RE, detraining and retraining. Indeed, after acute RE we identified 866 up- and 936 down-regulated genes at the expression level, with 270 (out of the 866 up-regulated) identified as being hypomethylated, and 216 (out of 936 downregulated) as hypermethylated. After chronic RE we identified 2,018 up- and 430 down-regulated genes with 592 (out of 2,018 upregulated) identified as being hypomethylated and 98 (out of 430 genes downregulated) as hypermethylated. After KEGG pathway analysis, genes associated with ‘cancer’ pathways were significantly enriched in both bioinformatic analysis of the pooled transcriptome and methylome datasets after both acute and chronic RE. This resulted in 23 (out of 69) and 28 (out of 49) upregulated and hypomethylated and 12 (out of 37) and 2 (out of 4) downregulated and hypermethylated ‘cancer’ genes following acute and chronic RE respectively. Within skeletal muscle tissue, these ‘cancer’ genes predominant functions were associated with matrix/actin structure and remodelling, mechano-transduction (e.g. PTK2/Focal Adhesion Kinase and Phospholipase D- following chronic RE), TGF-beta signalling and protein synthesis (e.g. GSK3B after acute RE). Interestingly, 51 genes were also identified to be up/downregulated in both the acute and chronic RE pooled transcriptome analysis as well as significantly hypo/hypermethylated after acute RE, chronic RE, detraining and retraining. Five genes; FLNB, MYH9, SRGAP1, SRGN, ZMIZ1 demonstrated increased gene expression in the acute and chronic RE transcriptome and also demonstrated hypomethylation in these conditions. Importantly, these 5 genes demonstrated retained hypomethylation even during detraining (following training induced hypertrophy) when exercise was ceased and lean mass returned to baseline (pre-training) levels, identifying them as genes associated with epigenetic memory in skeletal muscle. Importantly, for the first time across the transcriptome and epigenome combined, this study identifies novel differentially methylated genes associated with human skeletal muscle anaboli...

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Section: Discussionmentioning

confidence: 67%

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Turner

Seaborne

Sharples

2019

Sci Rep

143

View full text Add to dashboard Cite

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“…When a subclinical folate deficiency was created in postmenopausal women, plasma homocysteine increased and lymphocyte DNA methylation decreased (Jacob et al., 1998). Evidence from an animal study supports the importance of folate, as folic acid reduced the fat mass and serum glucose levels as well as improved insulin resistance in mice fed a high-fat diet (Li et al., 2018). Additionally, it altered the DNA methylation pattern of genes associated with obesity and T2D in adipose tissue of these mice.…”

Section: Main Textmentioning

confidence: 99%

Epigenetics in Human Obesity and Type 2 Diabetes

2019

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Epigenetic mechanisms control gene activity and the development of an organism. The epigenome includes DNA methylation, histone modifications, and RNA-mediated processes, and disruption of this balance may cause several pathologies and contribute to obesity and type 2 diabetes (T2D). This Review summarizes epigenetic signatures obtained from human tissues of relevance for metabolism—i.e., adipose tissue, skeletal muscle, pancreatic islets, liver, and blood—in relation to obesity and T2D. Although this research field is still young, these comprehensive data support not only a role for epigenetics in disease development, but also epigenetic alterations as a response to disease. Genetic predisposition, as well as aging, contribute to epigenetic variability, and several environmental factors, including exercise and diet, further interact with the human epigenome. The reversible nature of epigenetic modifications holds promise for future therapeutic strategies in obesity and T2D.

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“…While ADCY3 has no clearly defined role in skeletal muscle, it catalyzes the formation of the signalling molecule cAMP in response to G-protein signalling 42 , and regulates Ca 2+ -dependent insulin secretion. Its methylation has been demonstrated to change in adipose tissue in response to altered nutrition 43 , but no methylation data currently exists in skeletal muscle.…”

Section: Kegg Cancermentioning

confidence: 99%

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Turner

Seaborne

Sharples

2018

Preprint

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38Transcriptome wide changes in human skeletal muscle after acute (anabolic) and chronic resistance exercise 39 (RE) induced hypertrophy have been extensively determined in the literature. We have also recently 40 undertaken DNA methylome analysis (850,000 + CpG sites) in human skeletal muscle after acute and 41 chronic RE, detaining and retraining, where we identified an association between DNA methylation in an 42 epigenetic memory of exercise induced skeletal muscle hypertrophy. However, it is currently unknown as to 43 whether all the genes identified in the transcriptome studies to date are also epigenetically regulated at the 44 DNA level after acute, chronic or repeated RE exposure. We therefore aimed to undertake large scale 45 bioinformatical analysis by pooling the publicly available transcriptome data after acute (110 samples) and 46 chronic RE (181 samples) and comparing these large data sets with our genome-wide DNA methylation 47 analysis in human skeletal muscle after acute and chronic RE, detraining and retraining. Indeed, after acute 48 RE we identified 866 up-and 936 down-regulated genes at the expression level, with 270 (out of the 866 up-49 regulated) identified as being hypomethylated, and 216 (out of 936 downregulated) as hypermethylated. 50After chronic RE we identified 2,018 up-and 430 down-regulated genes with 592 (out of 2,018 upregulated) 51 identified as being hypomethylated and 98 (out of 430 genes downregulated) as hypermethylated. After 52 KEGG pathway analysis, genes associated with 'cancer' pathways were significantly enriched in both 53 bioinformatic analysis of the pooled transcriptome and methylome data after both acute and chronic RE. 54 This resulted in 23 (out of 69) and 28 (out of 49) upregulated and hypomethylated and 12 (out of 37) and 2 55 (out of 4) downregulated and hypermethylated 'cancer' genes following acute and chronic RE respectively. 56Within skeletal muscle tissue, these 'cancer' genes predominant functions were associated with matrix/ actin 57 structure and remodelling, mechano-transduction (including PTK2/Focal Adhesion Kinase and 58 Phospholipase D-following chronic RE only), TGF-beta signalling and protein synthesis (GSK3B after 59 acute RE only). Interestingly, 51 genes were also identified to be up/downregulated in both the acute and 60 chronic RE pooled transcriptome analysis as well as significantly hypo/hypermethylated after acute RE, 61 chronic RE, detraining and retraining. Five genes; FLNB, MYH9, SRGAP1, SRGN, ZMIZ1 demonstrated 62 increased gene expression in the acute and chronic RE transcriptome and also demonstrated 63 hypomethylation in these conditions. Importantly, these 5 genes demonstrated retained hypomethylation 64 even during detraining (following training induced hypertrophy) when exercise was ceased and lean mass 65 returned to baseline (pre-training) levels, identifying them as potential epigenetic memory genes. 66 Importantly, for the first time across the transcriptome and epigenome combined, this study identifies novel 67 diffe...

show abstract

Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice

Cited by 47 publications

References 48 publications

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Epigenetics in Human Obesity and Type 2 Diabetes

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

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