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Svensson, S.I.A.* ; Saeed, S.* ; Hoffmann, A. ; Ghosh, A.* ; Wolfrum, C.* ; Dahl, M.B.* ; Cayir, A.* ; Rønningen, T.* ; Bai, B.* ; Mala, T.* ; Kristinsson, J.A.* ; Kovacs, P.* ; Blüher, M. ; Valderhaug, T.G.* ; Böttcher, Y.*

HOOK1 gene expression and DNA methylation in obesity and related cardiometabolic traits.

Obes. Facts, DOI: 10.1159/000547603 (2025)
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Introduction: Accumulation of fat in omental visceral adipose tissue (OVAT) is strongly linked to metabolic diseases. Our recent findings show a distinct and more accessible chromatin landscape of the visceral depot compared to its subcutaneous counterpart. Based on integrated analysis of chromatin accessibility and transcriptomics, we identified previously unrecognised genes linked with obesity. Here, we performed in-depth analyses of one of the candidates, HOOK1, and tested for depot-specific gene expression, correlation with clinical traits and regulatory mechanisms including DNA methylation. Methods: We utilised intra-individually paired adipose tissue samples of human OVAT and subcutaneous adipose tissue (SAT) from our in-house cohort (N = 78). Gene expression was measured using real-time quantitative PCR and pyrosequencing was used to determine DNA methylation levels. Data were analysed for differential gene expression and DNA methylation differences between SAT and OVAT, along with correlation analyses with clinical variables related to obesity. Results were validated in adipose tissue samples from 1,618 donors of the Leipzig Obesity Biobank. Results: We observed consistently higher HOOK1 gene expression in OVAT compared to SAT and successfully confirmed this effect direction in several validation cohorts. We further identified that HOOK1 gene expression correlated with body mass index and hip circumference. We discovered a relationship between DNA methylation of the HOOK1 promoter with clinical variables important for liver function. Conclusion: Our data show that HOOK1 gene expression is adipose tissue depot-specific. We observed that gene expression and DNA methylation are correlated to clinical variables of obesity, suggesting that HOOK1 may play a role in obesity and its sequelae.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adipose Tissue ; Dna Methylation ; Epigenetics ; Gene Expression ; Obesity; Human Adipose-tissue; Cells
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1662-4025
e-ISSN 1662-4033
Journal Obesity Facts
Publisher Karger
Publishing Place Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-506501-001
Grants Deutsches Zentrum fur Diabetesforschung (DZD)
DFG (German Research Foundation)
University of Oslo
European Union
DOI 10.1159/000547603
WOS ID 001568503900001
Scopus ID 105015662481
Erfassungsdatum 2025-10-22
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