Assessment of Periprostatic and Subcutaneous Adipose Tissue Lipolysis and Adipocyte Size from Men with Localized Prostate Cancer.

Dushan Miladinovic,Colin H Cortie,Thomas Cusick,Barbara J Meyer,Kate L Mahon,Anne-Maree Haynes,Gary A Wittert,Andrew J Hoy,Lisa G Horvath,Phillip D Stricker,Lisa M Butler

doi:10.3390/cancers12061385

Abstract

The prostate is surrounded by periprostatic adipose tissue (PPAT), the thickness of which has been associated with more aggressive prostate cancer (PCa). There are limited data regarding the functional characteristics of PPAT, how it compares to subcutaneous adipose tissue (SAT), and whether in a setting of localized PCa, these traits are altered by obesity or disease aggressiveness. PPAT and SAT were collected from 60 men (age: 42–78 years, BMI: 21.3–35.6 kg/m2) undergoing total prostatectomy for PCa. Compared to SAT, adipocytes in PPAT were smaller, had the same basal rates of fatty acid release (lipolysis) yet released less polyunsaturated fatty acid species, and were more sensitive to isoproterenol-stimulated lipolysis. Basal lipolysis of PPAT was increased in men diagnosed with less aggressive PCa (Gleason score (GS) ≤ 3 + 4) compared to men with more aggressive PCa (GS ≥ 4 + 3) but no other measured adipocyte parameters related to PCa aggressiveness. Likewise, there was no difference in PPAT lipid biology between lean and obese men. In conclusion, lipid biological features of PPAT do differ from SAT; however, we did not observe any meaningful difference in ex vivo PPAT biology that is associated with PCa aggressiveness or obesity. As such, our findings do not support a relationship between altered PCa behavior in obese men and the metabolic reprogramming of PPAT.

Highlights

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in developed countries and the second most common cancer worldwide [1]
A hallmark feature of obesity is adipose tissue expansion and altered adipocyte fatty acid-triacylglycerol metabolism [37], and when combined with the reports that the amount of periprostatic adipose tissue (PPAT) correlates with higher grade or aggressiveness of disease, it is an attractive hypothesis that an adipose–prostate cancer (PCa) axis underpins these clinical observations in obese patients
Whilst we report a subtle difference in basal fatty acid release between less and more aggressive disease, there was no difference in the hormone-stimulated PPAT lipolysis

Summary

Introduction

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in developed countries and the second most common cancer worldwide [1]. Several studies have reported that PCa pathobiology is influenced by obesity, more aggressive carcinoma, poorer treatment outcomes, and increased cancer-specific mortality in obese men [2,3,4,5,6,7,8,9]. Significant attention has focused on the role that the local adipose bed that surrounds the prostate, called periprostatic adipose tissue (PPAT), plays in influencing PCa biology. A reciprocal interaction between adipocytes and PCa cells has been reported, both in terms of PPAT stimulating PCa aggressiveness and PCa cells altering adipocyte biology [18,19,20,21,22]. Direct tumor–adipocyte interaction does occur in vivo in multiple situations

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Conclusion