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| Status |
Public on Mar 08, 2016 |
| Title |
Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients [transcriptome analysis] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Type 2 diabetes is a complex disease associated with many underlying pathomechanisms. Epigenetic regulation of gene expression by DNA methylation has become increasingly recognized as an important component in the etiology of type 2 diabetes. We performed genome-wide methylome and transcriptome analysis in liver from severely obese patients with or without type 2 diabetes to discover aberrant pathways underlying the development of insulin resistance. We identified hypomethylation of five key genes involved in hepatic glycolysis, de novo lipogenesis and insulin resistance with concomitant increased mRNA expression and protein content. The CpG-site within the ATF-motif was hypomethylated in four of these genes in liver of non-diabetic and type 2 diabetic obese patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding. In conclusion, severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome and genes controlling glucose and lipid metabolism are hypomethylated at a regulatory site. Thus, obesity may epigenetically reprogram the liver towards increased lipid production and exacerbate the development of insulin resistance.
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| Overall design |
To better understand the molecular mechanisms underlying the development of hepatic insulin resistance and type 2 diabetes at a molecular level, we performed a genome-wide methylome and transcriptome analysis of liver from non-obese metabolically healthy, obese non-diabetic and obese type 2 diabetic patients. Distinct DNA methylation and gene expression profiles were identified in liver from the obese and type 2 diabetic patients compared with the non-obese participants.
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| Web link |
http://0-www-sciencedirect-com.brum.beds.ac.uk/science/article/pii/S2212877815002343
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| Contributor(s) |
Kirchner H, Sinha I, Gao H, Ruby MA, Schönke M, Lindvall JM, Barres R, Krook A, Näslund E, Dahlman-Wright K, Zierath JR |
| Citation(s) |
26977391 |
| Submission date |
Jan 15, 2015 |
| Last update date |
Nov 08, 2016 |
| Contact name |
Karin Dahlman-Wright |
| Organization name |
Karolinska Institutet
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| Department |
Department of Biosciences and Nutrition
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| Lab |
Medicinaren 25/Neo
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| Street address |
Blickagången 16
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| City |
Huddinge |
| ZIP/Postal code |
14157 |
| Country |
Sweden |
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| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (21)
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| This SubSeries is part of SuperSeries: |
| GSE65058 |
Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients |
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| Relations |
| BioProject |
PRJNA272669 |
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