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

Sadia Saeed·Anne Hoffmann·Stina Ingrid Alice Svensson·Tina Visnovska·Tobias Hagemann·Adhideb Ghosh·Christian Wolfrum·Akin Cayir·Tom Mala·Jon A Kristinsson·Matthias Blüher·Tone Gretland Valderhaug·Yvonne Böttcher
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Abstract

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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HumansConnexin 43FemaleMaleAdipose TissueMiddle AgedAdultHistone CodeEpigenesis, GeneticGene Expression ProfilingGene Expression RegulationObesityHistonesTranscriptomeAdipose tissueCardiometabolic healthEpigeneticsGene expressionJournal ArticleResearch Support, Non-U.S. Gov't

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Sadia Saeed, Anne Hoffmann, Stina Ingrid Alice Svensson, Tina Visnovska, Tobias Hagemann, Adhideb Ghosh, Christian Wolfrum, Akin Cayir, Tom Mala, Jon A Kristinsson, Matthias Blüher, Tone Gretland Valderhaug, Yvonne Böttcher. 2025-11-22. Integrative analysis of gene expression and histone modifications for DES, DSP, GJA1 and SMOC2 in adipose tissue reveals potential relationship to cardiometabolic health.. https://doi.org/10.1186/s10020-025-01391-3

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