Blood methylation pattern reflects epigenetic remodelling in adipose tissue after bariatric surgery

Abstract

Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood. Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N=6 female) with severe obesity pre- and post-surgery. The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from-11.5 to 10.8%; OVAT: 14,632 DMRs from-13.7 to 12.8%) than in blood (9267 DMRs from-8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery. Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors AT's inflammatory state post-bariatric surgery. The funding sources are listed in the Acknowledgments section.