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Saeed, S.* ; la Cour Poulsen, L.* ; Visnovska, T.* ; Hoffmann, A. ; Ghosh, A.* ; Wolfrum, C.* ; Rønningen, T.* ; Dahl, M.B.* ; Wang, J.* ; Cayir, A.* ; Mala, T.* ; Kristinsson, J.A.* ; Svanevik, M.* ; Hjelmesæth, J.* ; Hertel, J.K.* ; Blüher, M. ; Valderhaug, T.G.* ; Böttcher, Y.*

Chromatin landscape in paired human visceral and subcutaneous adipose tissue and its impact on clinical variables in obesity.

EBioMedicine 114:105653 (2025)

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BACKGROUND: Obesity is a global health challenge and adipose tissue exhibits distinct depot-specific characteristics impacting differentially on the risk of metabolic comorbidities. METHODS: Here, we integrate chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) data from intra-individually paired human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) samples to unveil depot-specific regulatory mechanisms. FINDINGS: We identified twice as many depot-specific differentially accessible regions (DARs) in OVAT compared to SAT. SAT-specific regions showed enrichment for adipose tissue enhancers involving genes controlling extracellular matrix organization and metabolic processes. In contrast, OVAT-specific regions showed enrichment in promoters linked to genes associated with cardiomyopathies. Moreover, OVAT-specific regions were enriched for bivalent transcription start site and repressive chromatin states, suggesting a "lingering" regulatory state. Motif analysis identified CTCF and BACH1 as most significantly enriched motifs in SAT and OVAT-specific DARs, respectively. Distinct gene sets correlated with important clinical variables of obesity, fat distribution measures, as well as insulin, glucose, and lipid metabolism. INTERPRETATION: We provide an integrated analysis of chromatin accessibility and transcriptional profiles in paired human SAT and OVAT samples, offering new insights into the regulatory landscape of adipose tissue and highlighting depot-specific mechanisms in obesity pathogenesis. FUNDING: SS received EU-Scientia postdoctoral Fellowship and project funding from the European Union's Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie Grant, (agreement No. 801133). LlCP and TR were supported by Helse Sør-Øst grants to Y.B (ID 2017079, ID 278908). MB received funding from grants from the DFG (German Research Foundation)-Projekt number 209933838-SFB 1052 (project B1) and by Deutsches Zentrum für Diabetesforschung (DZD, Grant: 82DZD00601).

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adipose Tissue ; Chromatin Accessibility ; Gene Expression ; Obesity

ISSN (print) / ISBN 2352-3964

e-ISSN 2352-3964

Journal EBioMedicine

Quellenangaben Volume: 114, Article Number: 105653

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)