| Autor: |
Henriette Kirchner, Indranil Sinha, Hui Gao, Maxwell A. Ruby, Milena Schönke, Jessica M. Lindvall, Romain Barrès, Anna Krook, Erik Näslund, Karin Dahlman-Wright, Juleen R. Zierath |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Molecular Metabolism, Vol 5, Iss 3, Pp 171-183 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2015.12.004 |
| Popis: |
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. Keywords: Liver, Obesity, Type 2 Diabetes, Epigenetics, Lipid, Glucose |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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