DNA methylation screening after roux-en Y gastric bypass reveals the epigenetic signature stems from genes related to the surgery per se

Abstract

Background/objectives Obesity has been associated with gene methylation regulation. Recent studies have shown that epigenetic signature plays a role in metabolic homeostasis after Roux-en Y gastric bypass (RYGB). To conduct a genome-wide epigenetic analysis in peripheral blood to investigate whether epigenetic changes following RYGB stem from weight loss or the surgical procedure per se. Subjects/methods By means of the Infinium Human Methylation 450 BeadChip array, global methylation was analyzed in blood of 24 severely obese women before and 6 months after RYGB and in 24 normal-weight women (controls). Results In blood cells, nine DMCpG sites showed low methylation levels before surgery, methylation levels increased after RYGB and neared the levels measured in the controls. Additionally, 44 CpG sites associated with the Wnt and p53 signaling pathways were always differently methylated in the severely obese patients as compared to the controls and were not influenced by RYGB. Finally, 1638 CpG sites related to inflammation, angiogenesis, and apoptosis presented distinct methylation in the post-surgery patients as compared to the controls. Conclusion Bariatric surgery per se acts on CpGs related to inflammation, angiogenesis, and endothelin-signaling. However, the gene cluster associated with obesity remains unchanged, suggesting that weight loss 6 months after RYGB surgery cannot promote this effect. Graphical abstract Electronic supplementary material The online version of this article (10.1186/s12920-019-0522-7) contains supplementary material, which is available to authorized users.

The effects of bariatric surgery on clinical profile, DNA methylation, and ageing in severely obese patients

“…We attempted to replicate our findings in two independent cohorts with similar data [34,35]. Cohort 1 included 11 severely obese patients (7 women and 4 men) who underwent Roux-en-Y gastric bypass (RYGB) surgery.…”

“…Cohort 2 included 24 severely obese women, who also underwent RYGB. Normalized DNA methylation beta values and phenotype data before and 6 months after the surgery was obtained from the authors of the study [35]. First, we performed EWAS using the same method as described above.…”

Altered pathways in methylome and transcriptome longitudinal analysis of normal weight and bariatric surgery women

“…Study participants. The present study included 24 normal weight women (BMI: 22.5 ± 1.6 kg/m 2 , 36.9 ± 11.8 years) and 24 severe obese women (BMI: 43.3 ± 5.7 kg/m 2 , 36.9 ± 10.2 years) submitted to RYGB which methylation and gene expression profile had been analyzed previously 20,21 . All samples from obese women were collected at preoperative time and after 6 months of bariatric surgery.…”

“…Genome-wide methylation analysis was conducted using the Infinium Human Methylation 450 BeadChip (Illumina, San Diego, CA, USA). Beadchips were scanned with the Illumina iScanSQ system and DNA quality checks, bisulfite modification, hybridization, data normalization, and statistical filter were performed as described before 21 .…”

“…Before comparing gene expression and methylation analysis, a correction by cellular type was made in DNA methylation data (Supplementary Table 1). By crossing and comparing the differentially regulated gene (DEG) and differentially methylated genes (DMG), the list generated from the gene expression analysis 21 were overlapped with the lists from the methylation analysis 20 using Venn diagram (http://bioinfogp.cnb.csic.es/tools/venny/). Figure 2 shows a schematic diagram of integrative analysis of methylation and expression arrays.…”