HOOK1 Gene Expression and DNA Methylation in Obesity and Related Cardiometabolic Traits

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.

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.

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.

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.