Blood methylation pattern reflects epigenetic remodelling in adipose tissue after bariatric surgeryResearch in context
Luise Müller,
Anne Hoffmann,
Stephan H. Bernhart,
Adhideb Ghosh,
Jiawei Zhong,
Tobias Hagemann,
Wenfei Sun,
Hua Dong,
Falko Noé,
Christian Wolfrum,
Arne Dietrich,
Michael Stumvoll,
Lucas Massier,
Matthias Blüher,
Peter Kovacs,
Rima Chakaroun,
Maria Keller
Affiliations
Luise Müller
Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany
Anne Hoffmann
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany
Stephan H. Bernhart
Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107, Leipzig, Germany; Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany; Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, 04107, Leipzig, Germany
Adhideb Ghosh
Institute of Food, Nutrition and Health, ETH Zurich, 8092, Schwerzenbach, Switzerland
Jiawei Zhong
Department of Medicine Huddinge (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, 141 83, Huddinge, Sweden
Tobias Hagemann
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany
Wenfei Sun
Institute of Food, Nutrition and Health, ETH Zurich, 8092, Schwerzenbach, Switzerland
Hua Dong
Institute of Food, Nutrition and Health, ETH Zurich, 8092, Schwerzenbach, Switzerland
Falko Noé
Institute of Food, Nutrition and Health, ETH Zurich, 8092, Schwerzenbach, Switzerland
Christian Wolfrum
Institute of Food, Nutrition and Health, ETH Zurich, 8092, Schwerzenbach, Switzerland
Arne Dietrich
Leipzig University Hospital, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Section of Bariatric Surgery, 04103, Leipzig, Germany
Michael Stumvoll
Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany; Deutsches Zentrum für Diabetesforschung e.V., 85764, Neuherberg, Germany
Lucas Massier
Department of Medicine Huddinge (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, 141 83, Huddinge, Sweden
Matthias Blüher
Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany; Deutsches Zentrum für Diabetesforschung e.V., 85764, Neuherberg, Germany
Peter Kovacs
Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany; Deutsches Zentrum für Diabetesforschung e.V., 85764, Neuherberg, Germany
Rima Chakaroun
Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany; The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden
Maria Keller
Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, 04103, Germany; Corresponding author. Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Philipp-Rosenthal Str. 27, D-04103, Leipzig, Germany.
Summary: 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.
