Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

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Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients. / Kirchner, Henriette; Sinha, Indranil; Gao, Hui; Ruby, Maxwell A; Schönke, Milena; Lindvall, Jessica M; Barrès, Romain; Krook, Anna; Näslund, Erik; Dahlman-Wright, Karin; Zierath, Juleen R.

In: Molecular Metabolism, Vol. 5, No. 3, 03.2016, p. 171-83.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kirchner, H, Sinha, I, Gao, H, Ruby, MA, Schönke, M, Lindvall, JM, Barrès, R, Krook, A, Näslund, E, Dahlman-Wright, K & Zierath, JR 2016, 'Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients', Molecular Metabolism, vol. 5, no. 3, pp. 171-83. https://doi.org/10.1016/j.molmet.2015.12.004

APA

Kirchner, H., Sinha, I., Gao, H., Ruby, M. A., Schönke, M., Lindvall, J. M., Barrès, R., Krook, A., Näslund, E., Dahlman-Wright, K., & Zierath, J. R. (2016). Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients. Molecular Metabolism, 5(3), 171-83. https://doi.org/10.1016/j.molmet.2015.12.004

Vancouver

Kirchner H, Sinha I, Gao H, Ruby MA, Schönke M, Lindvall JM et al. Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients. Molecular Metabolism. 2016 Mar;5(3):171-83. https://doi.org/10.1016/j.molmet.2015.12.004

Author

Kirchner, Henriette ; Sinha, Indranil ; Gao, Hui ; Ruby, Maxwell A ; Schönke, Milena ; Lindvall, Jessica M ; Barrès, Romain ; Krook, Anna ; Näslund, Erik ; Dahlman-Wright, Karin ; Zierath, Juleen R. / Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients. In: Molecular Metabolism. 2016 ; Vol. 5, No. 3. pp. 171-83.

Bibtex

@article{435050c29c9c40a4a00997e50b8583f7,
title = "Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients",
abstract = "OBJECTIVE: Epigenetic modifications contribute to the etiology of type 2 diabetes.METHOD: We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without type 2 diabetes and non-obese men to discover aberrant pathways underlying the development of insulin resistance. Results were validated by pyrosequencing.RESULT: We identified hypomethylation of genes involved in hepatic glycolysis and insulin resistance, concomitant with increased mRNA expression and protein levels. Pyrosequencing revealed the CpG-site within ATF-motifs was hypomethylated in four of these genes in liver of severely obese non-diabetic and type 2 diabetic patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding.CONCLUSION: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance.",
author = "Henriette Kirchner and Indranil Sinha and Hui Gao and Ruby, {Maxwell A} and Milena Sch{\"o}nke and Lindvall, {Jessica M} and Romain Barr{\`e}s and Anna Krook and Erik N{\"a}slund and Karin Dahlman-Wright and Zierath, {Juleen R}",
year = "2016",
month = mar,
doi = "10.1016/j.molmet.2015.12.004",
language = "English",
volume = "5",
pages = "171--83",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

AU - Kirchner, Henriette

AU - Sinha, Indranil

AU - Gao, Hui

AU - Ruby, Maxwell A

AU - Schönke, Milena

AU - Lindvall, Jessica M

AU - Barrès, Romain

AU - Krook, Anna

AU - Näslund, Erik

AU - Dahlman-Wright, Karin

AU - Zierath, Juleen R

PY - 2016/3

Y1 - 2016/3

N2 - OBJECTIVE: Epigenetic modifications contribute to the etiology of type 2 diabetes.METHOD: We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without type 2 diabetes and non-obese men to discover aberrant pathways underlying the development of insulin resistance. Results were validated by pyrosequencing.RESULT: We identified hypomethylation of genes involved in hepatic glycolysis and insulin resistance, concomitant with increased mRNA expression and protein levels. Pyrosequencing revealed the CpG-site within ATF-motifs was hypomethylated in four of these genes in liver of severely obese non-diabetic and type 2 diabetic patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding.CONCLUSION: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance.

AB - OBJECTIVE: Epigenetic modifications contribute to the etiology of type 2 diabetes.METHOD: We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without type 2 diabetes and non-obese men to discover aberrant pathways underlying the development of insulin resistance. Results were validated by pyrosequencing.RESULT: We identified hypomethylation of genes involved in hepatic glycolysis and insulin resistance, concomitant with increased mRNA expression and protein levels. Pyrosequencing revealed the CpG-site within ATF-motifs was hypomethylated in four of these genes in liver of severely obese non-diabetic and type 2 diabetic patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding.CONCLUSION: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance.

U2 - 10.1016/j.molmet.2015.12.004

DO - 10.1016/j.molmet.2015.12.004

M3 - Journal article

C2 - 26977391

VL - 5

SP - 171

EP - 183

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

IS - 3

ER -

ID: 159743545