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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)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adipose Tissue ; Chromatin Accessibility ; Gene Expression ; Obesity; Diet-induced Obesity; Gene-expression; Transcription Factor; Weight-loss; Rna-seq; Methylation; Accessibility; Association; Activation; Deposition
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2352-3964
e-ISSN 2352-3964
Zeitschrift EBioMedicine
Quellenangaben Band: 114, Heft: , Seiten: , Artikelnummer: 105653 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-506501-001
Förderungen Deutsches Zentrum fuer Diabetesforschung (DZD)
DFG (German Research Foundation)
Helse Sr-Ost
European Union
EU-Scientia
DOI 10.1016/j.ebiom.2025.105653
WOS ID 001467774200001
PubMed ID 40118008
Erfassungsdatum 2025-05-09
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