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 and Zierath, Juleen R (2016) Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients. Molecular Metabolism, 5 (3). pp. 171-183. ISSN 2212-8778

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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.

Item Type: Article
Uncontrolled Keywords: liver,obesity,type 2 diabetes,epigenetics,lipid,glucose
Depositing User: Pure Connector
Date Deposited: 23 Jan 2018 15:30
Last Modified: 30 Sep 2020 23:48
URI: https://ueaeprints.uea.ac.uk/id/eprint/66052
DOI: 10.1016/j.molmet.2015.12.004

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