Periprostatic adipose tissue displays a chronic hypoxic state that limits its expandability

International audienceWhite adipose tissue accumulates at various sites throughout the body and some adipose tissue depots exist in close proximity to organs, whose function they could influence in a paracrine manner. Prostate gland is surrounded by a poorly characterized adipose depot called periprostatic adipose tissue (PPAT) playing emerging roles in prostate-related disorders. Unlike all other adipose depots, PPAT secretes pro-inflammatory cytokines even in lean individuals and does not increase in volume during obesity. These unique features remain unexplained due to the poor structural and functional characterization of this tissue. We characterized the structural organization of PPAT in patients in comparison to abdominopelvic adipose tissue (APAT), an extraperitoneal adipose depot whose accumulation is correlated to BMI. Confocal microscopy followed by 3D reconstructions showed a sparse vascular network in PPAT when compared with that in APAT, suggesting that this tissue is hypoxic. Unbiased comparisons of PPAT and APAT transcriptomes found that most differentially expressed genes were related to the hypoxia response. High levels of the hypoxia-inducible factor HIF-2α confirmed the presence of an adaptive response to hypoxia in PPAT. This chronic hypoxic state was associated with inflammation and fibrosis, which were not further upregulated by obesity. This fibrosis and inflammation explain the failure of PPAT to expand in obesity and open new mechanistic avenues to explain its role in prostate-related disorders including cance