Periprostatic Adipose Tissue Displays a Chronic Hypoxic State that Limits Its Expandability

Area of Science:

• Adipose tissue biology
• Prostate pathology
• Vascular biology

Background:

• Periprostatic adipose tissue (PPAT) surrounds the prostate gland and influences its function.
• PPAT exhibits unique characteristics, including constitutive inflammation and lack of obesity-related expansion.
• The structural and functional basis for these unique PPAT features is poorly understood.

Purpose of the Study:

• To structurally and functionally characterize PPAT in comparison to abdominopelvic adipose tissue (APAT).
• To investigate the underlying mechanisms for PPAT's unique inflammatory and non-expansile properties.

Main Methods:

• Comparative analysis of PPAT and APAT from patients.
• Confocal microscopy and 3D reconstruction to assess vascular networks.
• Transcriptome analysis to identify differentially expressed genes.
• Assessment of hypoxia-inducible factor 2α (HIF-2α) levels.

Main Results:

• PPAT exhibits a significantly sparser vascular network compared to APAT, indicating hypoxia.
• Transcriptomic analysis revealed widespread hypoxia response genes in PPAT.
• Elevated HIF-2α levels confirmed an adaptive response to chronic hypoxia in PPAT.
• Chronic hypoxia in PPAT is associated with inflammation and fibrosis, independent of obesity.

Conclusions:

• PPAT's unique structural and functional characteristics are driven by chronic hypoxia.
• The associated inflammation and fibrosis explain PPAT's failure to expand in obesity.
• These findings provide mechanistic insights into PPAT's role in prostate disorders, including cancer.