Depot-specific differences in visceral and subcutaneous adipose tissue from patients with obesity

Factors limiting fat cell expandability remain scarcely explored, and comprehensive functional comparisons of adipose depots in humans are limited. In the present study, we collected visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) paired-samples from 22 patients with obesity undergoing elective Roux-en-Y gastric bypass surgery. Whole tissue samples were used to determine adipocyte cell size using a coulter counter and gene expression levels using bulk mRNA sequencing. Isolated adipocytes from the same tissue samples were used to functionally assess glucose uptake using glucose tracer assay, and lipolysis by measuring glycerol release. Western blotting was used to determine Caveolin 1 levels in adipocytes. The relationship between COL3A1 expression and systemic health outcomes was assessed using data from the Adipose Tissue Knowledge Portal. We found that SAT adipocytes were larger in size, displayed higher basal lipolysis and higher lipolysis-related gene expression than VAT adipocytes. Isoprenaline-induced lipolytic responsiveness, as well as basal and insulin-stimulated glucose uptake were higher in VAT than in SAT adipocytes. SAT displayed higher levels of extracellular matrix components associated with cellular flexibility and higher cellular Caveolin 1 levels than VAT. Further, we identified subcutaneous adipose tissue COL3A1 as a potential contributor to insulin resistance in obesity, positively associated with BMI, HOMA-IR and adipocyte size. In summary, our findings underscore distinct metabolic properties of subcutaneous and visceral adipocytes in obesity, with SAT adipose tissue exhibiting characteristics that possibly promote greater cellular expandability.