Diabetologie und Stoffwechsel 2015; 10 - FV3
DOI: 10.1055/s-0035-1549509

Genome wide DNA promoter methylation: Differences in human subcutaneous vs. omental visceral adipose tissue

M Keller 1, L Hopp 2, XL Liu 1, K Rohde 1, M Klös 1, A Dietrich 3, MR Schön 4, D Gärtner 4, T Lohmann 5, M Dreßler 5, M Stumvoll 1, 6, P Kovacs 1, H Binder 2, M Blüher 6, Y Böttcher 1
  • 1Universität Leipzig, IFB Adipositas Erkrankungen, Leipzig, Germany
  • 2Universität Leipzig, Interdisziplinäres Zentrum für Bioinformatik, Leipzig, Germany
  • 3Universität Leipzig, Department für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Leipzig, Germany
  • 4Städt. Klinikum Karlsruhe, Klinik für Viszeral Chirurgie, Karlsruhe, Germany
  • 5Städt. Klinikum Dresden-Neustadt, Dresden, Germany
  • 6Universität Leipzig, Department für Medizin, Leipzig, Germany

Background: Differences in DNA methylation pattern between subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) may help, together with corresponding changes in the mRNA profile, to elucidate variances in metabolic activity. In the present study we examined genome wide promoter methylation and mRNA expression pattern in 80 paired human SAT and OVAT samples including lean as well as obese subjects.

Methods: DNA methylation analysis was performed using methylated DNA immunoprecipitation and subsequent hybridising on Affymetrix Human Promoter 1.0R tilling arrays. Expression profiles were generated using Illunima human HT-12 chips. All genes with at least 30% methylation difference between SAT and OVAT or lean and obese subjects in the same fat depot were taken forward to overlap analysis with corresponding mRNA expression levels.

Results: We identified 35 genes in the lean and 38 in the obese subgroup conferring negative correlation between DNA methylation and mRNA expression comparing SAT and OVAT. 37 genes were found in the SAT and 76 in the OVAT subgroup comparing lean and obese individuals. The gene lists included known candidate genes such as PPARG but also unexpected genes, e.g. BHMT.

Conclusion: To the best of our knowledge, we show the first genome wide epigenetic data set comparing SAT and OVAT in a considerably large cohort. We identified significant differences in genome wide DNA methylation pattern in paired human SAT and OVAT samples from lean and obese subjects with corresponding changes in mRNA levels. This work helped to identify novel interesting genes related to human obesity.