Fat distribution in women associates with depot-specific transcriptomics signatures and chromatin structure

Preferential accumulation of fat in the upper body (apple shape) is associated with higher risk of developing metabolic syndrome relative to lower body fat (pear shape). We previously discovered that chromatin openness defined partially the transcriptome of pre-adipocytes isolated from abdominal and gluteofemoral fat. However, the molecular mechanisms underlying inter individual fat repartition variation are unknown. Adipocyte fraction was isolated from abdominal and gluteofemoral fat biopsies of premenopausal women (age and BMI-matched) segregated initially only by their waist to hip ratio. We evaluated transcriptomic and chromatin accessibility using RNA-seq and ATAC-seq along with key clinical parameters. Our data showed that higher lower body fat mass was associated with better lipid profile and free fatty acid turnover after glucose administration. Lipid and glucose metabolic pathways genes were expressed at higher levels in gluteofemoral adipocyte fraction in pears, while genes as...