Login to Access Video or Poster Abstract: MP17-18
Sources of Funding: None

Introduction

Periprostatic fat (PPF) is a well-vascularized adipose tissue that encloses the prostate containing resident adipose tissue macrophages (ATM) that are mobilized and recruited to areas with high tissue remodeling. PPF can secrete a wide range of adipokines involved in physiologic and pathologic processes. It is well established that the unbalanced production of pro-inflammatory adipokines is a key component to the development of the metabolic syndrome, a risk factor for lower urinary tract symptoms (LUTS) and BPH progression. However, the link between PPF and BPH pathogenesis has not been previously addressed. In this study, we hypothesize that during BPH progression, PPF secretes a pro-inflammatory cytokine profile leading to chronic activation of NF-&[kappa]B signaling pathway

Methods

PPF was collected from patients undergoing prostatectomy. The thickness of PPF was determined (distance between the pubic symphysis and prostate) in 205 patients using MRI and classified based on their BMI (lean vs. obese). The composition of PPF was characterized histopathologically with emphasis on the immune/inflammatory infiltrates. To determine the factors secreted by PPF, a short in vitro culture was used to generated conditioned medium and adipocytokine array analysis performed. Proliferation of benign prostate epithelial and stromal cells exposed to PPF-CM was assessed. Upon exposure to PPF-CM, activation of the NF-&[kappa]B pathway was determined by western blot analysis. In vivo experiments were performed xenografting PPF and human prostate tissues under the kidney capsule of SCID mice to determine the effects of PPF on prostate histology and recruitment of inflammatory cells

Results

Histological analysis of human PPF samples showed an increased ratio of multilocular/unilocular phenotype composed mainly of macrophages and mononuclear infiltrates in obese individuals compared to the unilocular pattern and lack of inflammatory infiltrates in lean patients. Obese patients showed a significantly increased PPF thickness (more than double) compared to lean patients. Interestingly MRI showed that PPF only partially surrounds the prostate in lean patients, while fat tissue almost completely encased the prostate in obese individuals. Adipokine array assays from PPF-CM samples show the expression of a profile of pro-inflammatory factors. Addition of androgens modulated the secretion of IL11, TGFβ1, IL16 and SDF1α, among oth

Conclusions

Our preliminary studies suggest a potential role for the PPF pro-inflammatory secretome in BPH pathogenesis

Funding

None