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Series GSE65057 Query DataSets for GSE65057
Status Public on Mar 08, 2016
Title Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients [methylome analysis]
Organism Homo sapiens
Experiment type Methylation profiling by array
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.
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.
Web link
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 16, 2015
Last update date Mar 22, 2019
Contact name Karin Dahlman-Wright
Organization name Karolinska Institutet
Department Department of Biosciences and Nutrition
Lab Medicinaren 25/Neo
Street address Blickagången 16
City Huddinge
ZIP/Postal code 14157
Country Sweden
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (24)
GSM1586513 BEA1: 8691803111_A1_ND-obese
GSM1586514 BEA2: 8691803111_A2_T2D-obese
GSM1586515 BEA3: 8691803111_A3_T2D-obese
This SubSeries is part of SuperSeries:
GSE65058 Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients
BioProject PRJNA272810

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65057_RAW.tar 381.0 Mb (http)(custom) TAR (of IDAT)
GSE65057_signal_intensities.txt.gz 140.1 Mb (ftp)(http) TXT
Processed data included within Sample table

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