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Series GSE24884 Query DataSets for GSE24884
Status Public on Feb 09, 2017
Title Methylation RIKEN-cohort
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary BACKGROUND:
Obesity is associated with changes in fat cell gene expression and metabolism. What drives these changes is not well understood. We aimed to explore fat cell epigenetics, i.e., DNA methylation, as one mediator of gene regulation, in obese women. The global DNA methylome for abdominal subcutaneous fat cells was compared between 15 obese case (BMI 41.4?±?4.4 kg/m(2), mean?±?SD) and 14 never-obese control women (BMI 25.2?±?2.5 kg/m(2)). Global array-based transcriptome analysis was analyzed for subcutaneous white adipose tissue (WAT) from 11 obese and 9 never-obese women. Limma was used for statistical analysis.
RESULTS:
We identified 5529 differentially methylated DNA sites (DMS) for 2223 differentially expressed genes between obese cases and never-obese controls (false discovery rate <5 %). The 5529 DMS displayed a median difference in beta value of 0.09 (range 0.01 to 0.40) between groups. DMS were under-represented in CpG islands and in promoter regions, and over-represented in open sea-regions and gene bodies. The 2223 differentially expressed genes with DMS were over-represented in key fat cell pathways: 31 of 130 (25 %) genes linked to "adipogenesis" (adjusted P?=?1.66?×?10(-11)), 31 of 163 (19 %) genes linked to "insulin signaling" (adjusted P?=?1.91?×?10(-9)), and 18 of 67 (27 %) of genes linked to "lipolysis" (P?=?6.1?×?10(-5)). In most cases, gene expression and DMS displayed reciprocal changes in obese women. Furthermore, among 99 candidate genes in genetic loci associated with body fat distribution in genome-wide association studies (GWAS); 22 genes displayed differential expression accompanied by DMS in obese versus never-obese women (P?=?0.0002), supporting the notion that a significant proportion of gene loci linked to fat distribution are epigenetically regulated.
CONCLUSIONS:
Subcutaneous WAT from obese women is characterized by congruent changes in DNA methylation and expression of genes linked to generation, distribution, and metabolic function of fat cells. These alterations may contribute to obesity-associated metabolic disturbances such as insulin resistance in women.
 
Overall design Abdominal subcutaneous adipose needle biopsies were obtained from women (n=56) with a wide variation in BMI. From the biopsies we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.0 ST Arrays (Affymetrix Inc., Santa Clara, CA), labelled RNA to Affymetrix miRNA arrays, and bisulphite converted DNA to Illumina Infinium HumanMethylation27 beadchips using standardised protocols (Affymetrix Inc., Illumina Inc.) . Subsequent analyses of gene expression was performed using the Affymetrix GeneChip Operating Software version 1.4. To allow comparisons of transcript levels between samples, all samples were subjected to an all-probeset scaling-to-target signal of 100. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. Subsequent analyses were performed using Genome Studio Methylation Module 1.0 (Illumina Inc.)
 
Contributor(s) Mejhert N, Arner E, Dahlman I, Arner P
Citation(s) 26351548
Submission date Oct 22, 2010
Last update date Feb 09, 2017
Contact name Ingrid Dahlman
E-mail(s) ingrid.dahlman@ki.se
Organization name Karolinska
Street address Karolinska Huddinge
City Stockholm
ZIP/Postal code 14186
Country Sweden
 
Platforms (1)
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (56)
GSM611971 genomic DNA from white adipose tissue nonobese_83
GSM611972 genomic DNA from white adipose tissue nonobese_3664
GSM611973 genomic DNA from white adipose tissue Obese_2636
Relations
BioProject PRJNA132029

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
GSE24884_RAW.tar 5.8 Mb (http)(custom) TAR
GSE24884_non_normalized.txt.gz 8.3 Mb (ftp)(http) TXT
Processed data included within Sample table
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