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| Status |
Public on May 06, 2015 |
| Title |
The fat cell epigenetic signature in post-obese women is characterized by global hypomethylation and differential DNA methylation of adipogenesis genes |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Background/Objectives: Obese subjects have increased number of enlarged fat cells which are reduced in size but not number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity.
Subjects/Methods: Genome-wide DNA methylation was analyzed in abdominal subcutaneous fat cells from 16 women examined two years after gastric bypass surgery at a post-obese state (BMI 26±2 kg/m2, mean±s.d.) and 14 never-obese women (BMI 25±2 kg/m2). Gene expression was analyzed in subcutaneous adipose tissue from 9 women in each group. In a secondary analysis, we examined DNA methylation and expression of adipogenesis genes in 15 and 11 obese women, respectively.
Results: The average degree of DNA methylation of all analyzed CpG-sites was lower in fat cells from post-obese as compared to never-obese women (P=0.014). 8,504 CpG sites were differentially methylated in fat cells from post-obese versus never-obese women (false discovery rate 1%). DMS were under-represented in CpG-islands and surrounding shores. The 8,504 DMS mapped to 3,717 unique genes; these genes were over-represented in cell differentiation pathways. Notably, 27% of genes linked to adipogenesis (i.e. 35 of 130) displayed DMS (adjusted P=10−8) in post-obese versus never-obese women. Next, we explored DNA methylation and expression of genes linked to adipogenesis in more detail in adipose tissue samples. DMS annotated to adipogenesis genes were not accompanied by differential gene expression in post-obese compared to never-obese women. In contrast, adipogenesis genes displayed differential DNA methylation accompanied by altered expression in obese women,
Conclusions: Global CpG hypomethylation and overrepresentation of DMS in adipogenesis genes in fat cells may contribute to adipose hyperplasia in post-obese women.
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| Overall design |
Post obese=16, Control group=14.
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| Contributor(s) |
Dahlman I, Sinha I, Gao H, Brodin D, Thorell A, Rydén M, Andersson DP, Henriksson J, Perfilyev A, Ling C, Dahlman-Wright K, Arner P |
| Citation(s) |
25783037 |
| Submission date |
Jun 18, 2014 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Ingrid Dahlman |
| E-mail(s) |
indranil.sinha.2@ki.se
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| Organization name |
Karolinska Institute
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| Department |
Department of Medicine
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| Street address |
Hälsovägen 7
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| City |
Huddinge |
| ZIP/Postal code |
14157 |
| Country |
Sweden |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA253039 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE58622_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
| GSE58622_signal_intensities.txt.gz |
167.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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