24 The effect of bariatric surgery on DNA methylation in blood and omental visceral adipose tissue

Zusammenfassung

In this study, we show that DNA methylation changes are associated with differential gene expression and the phenotypic improvements after bariatric surgery. Further studies are ongoing addressing long-term methylation changes of candidate sites after surgery, which helps to explore the role of DNA methylation on beneficial effects of bariatric surgery.

Einleitung

Metabolic surgery is currently the most effective treatment option to achieve long-term weight loss in patients with obesity. The subsequent metabolic improvements often occur independent of weight loss, whereby molecular mechanisms are not fully understood yet. Since modifications in DNA methylation patterns have been evidenced after metabolic surgery, we aimed to explore methylation signatures in blood and adipose tissue associated with metabolic improvements. In addition, we investigated whether methylation changes in adipose tissue are related to variability in gene expression.

Material und Methodik

Genome wide DNA methylation in blood (N=30) and omental visceral adipose tissue from 2-step surgical approach (OVAT) (N=4) was analyzed in patients with severe obesity using Illumina 850K EPIC technology before and after bariatric surgery (blood 24 months, OVAT 15 months). Transcriptome changes in OVAT were analyzed in parallel using RNA sequencing. Identified differentially methylated regions (DMRs) were tested for associations with phenotype changes, as well as with gene expression changes in OVAT. Differentially methylated and expressed genes were analyzed for KEGG pathway enrichment.

Ergebnisse

Comparing pre- and post-surgery, we identified 1136 DMRs (FDR<1%, |meth. diff.|>1%) in blood relating to 694 unique genes. Mean methylation changes of most significant DMRs in blood correlated with BMI change (FGFR2, PTPRN2), plasma insulin (FZD7), HDL-cholesterol (PM20D1) and circulating triglycerides (DUSP22). In OVAT we identified 646 DMRs (FDR<1%, |meth. diff.|>10%) relating to 436 unique genes. DNA methylation in adipose tissue was more strongly affected by bariatric surgery (ranging from −25% to 17%) than blood (−4 to 4%). From 469 differentially expressed genes (DEGs) (FDR<1%, |log₂ fold change|>2) in OVAT, 119 also showed differential methylation (FDR<1%, |meth.diff.|>10%). Pathway enrichment analysis of DEGs revealed a significant enrichment of upregulated genes in the FoxO signaling pathway, and enrichment of downregulated genes in several immune signaling pathways.

Publikationsverlauf

Artikel online veröffentlicht:
24. September 2021