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Saeed, S.* ; Hoffmann, A. ; Svensson, S.I.A.* ; Visnovska, T.* ; Hagemann, T. ; Ghosh, A.* ; Wolfrum, C.* ; Cayir, A.* ; Mala, T.* ; Kristinsson, J.A.* ; Blüher, M. ; Valderhaug, T.G.* ; Böttcher, Y.*

Integrative analysis of gene expression and histone modifications for DES, DSP, GJA1 and SMOC2 in adipose tissue reveals potential relationship to cardiometabolic health.

Mol. Med., DOI: 10.1186/s10020-025-01391-3 (2025)
Postprint DOI PMC
Open Access Green
Creative Commons Lizenzvertrag
BACKGROUND: Adipose tissue influences cardiometabolic health through its endocrine activity and its role in regulating inflammation, lipid metabolism, and cardiovascular function. The expression of cardiac-associated genes within adipose tissue may reflect or contribute to cardiometabolic risk, yet this relationship remains poorly understood. This study investigates the expression profiles of the cardiac function associated genes GJA1, DES, DSP and SMOC2 in human adipose tissue, and analyses their associations with cardiometabolic traits. Additionally, we explore epigenomic mechanisms that may underlie their differential gene expression. METHODS: Expression profiling and functional enrichment analyses were conducted to identify depot-specific cardiac gene expression patterns. Quantitative PCR validated gene expression in paired subcutaneous (SAT) and omental visceral adipose tissue (OVAT) samples from 78 individuals with obesity. Gene expression was further validated in three independent cohorts (N = 1,548 total). Associations with clinical traits were assessed using Spearman correlations and multivariate linear regression, adjusted for age, sex, and BMI. Integration with transcriptomic and proteomic datasets publicly available from the Adipose Tissue Knowledge Portal was performed to strengthen clinical relevance. Epigenomic profiling using genome-wide ChIP-seq for histone marks (H3K4me3, H3K4me1, H3K27ac, H3K27me3) was conducted in paired SAT and OVAT samples from five individuals. RESULTS: DES, DSP, GJA1, and SMOC2 were significantly upregulated in OVAT compared to SAT. DES, DSP, and SMOC2 showed consistent expression patterns across all cohorts, while GJA1 exhibited context-dependent regulation. Gene expression in SAT was negatively correlated with cardiometabolic traits, including blood pressure, insulin resistance, and liver function markers. These associations were confirmed by regression analysis and supported by publicly available multi-omics data. Epigenetic analyses revealed OVAT-specific enrichment of active histone marks and reduced repressive marks, supporting higher differential transcriptional activity in OVAT. CONCLUSIONS: Depot-specific gene expression of DES, DSP, and SMOC2 in adipose tissue is robustly linked to cardiometabolic traits and supported by distinct epigenetic landscapes in OVAT vs SAT, highlighting their potential as novel biomarkers for cardiometabolic health.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adipose Tissue ; Cardiometabolic Health ; Epigenetics ; Gene Expression ; Obesity
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 1076-1551
e-ISSN 1435-8123
Zeitschrift Molecular Medicine
Verlag Feinstein Inst. for Medical Research
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
DOI 10.1186/s10020-025-01391-3
PubMed ID 41275133
Erfassungsdatum 2025-11-26
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