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Müller, L.* ; Hoffmann, A. ; Bernhart, S.H.* ; Ghosh, A.* ; Zhong, J.* ; Hagemann, T. ; Sun, W.* ; Dong, H.* ; Noé, F.* ; Wolfrum, C.* ; Dietrich, A.* ; Stumvoll, M. ; Massier, L.* ; Blüher, M. ; Kovacs, P.* ; Chakaroun, R.* ; Keller, M.

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

EBioMedicine 106:105242 (2024)

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	Open Access Gold

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BACKGROUND: 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. METHODS: 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. FINDINGS: 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, 49 regions 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. INTERPRETATION: 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. FUNDING: The funding sources are listed in the Acknowledgments section.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adipose Tissue ; Bariatric Surgery ; Blood ; Dna Methylation ; Dna Methylation Age ; Inflammation; Body-mass Index; Dna Methylation; Promoter Methylation; Weight-loss; Obesity; Bcap; Association; Overweight; Resistance; Receptor

ISSN (print) / ISBN 2352-3964

e-ISSN 2352-3964

Journal EBioMedicine

Quellenangaben Volume: 106, Article Number: 105242

Publisher Elsevier

Publishing Place Amsterdam [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants Walther-Benjamin fellowship from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Deutsches Zentrum fur Diabetesforschung (DZD)
German Federal Ministry of Health (Berlin, Germany)
Ministry of Culture and Science of the state North Rhine-Westphalia (Dusseldorf, Germany)
German Federal Ministry of Education and Research (BMBF) through the German Center for Diabetes Research (DZD e.V.)
SSMF (SvenskaSallskapet for Medicinsk Forskning)
VR (Vetenskapsradet)
BMBF through Medical Faculty, University of Leipzig
Federal Ministry of Education and Research (BMBF), Germany
European Union
DFG (German Research Foundation)