Poster Presentation 2nd Australian Cancer and Metabolism Meeting 2017

Analysis of Basal and Hormone-Stimulated Lipolysis of Peri-Prostatic Adipose Tissue from Men with Localised Prostate Cancer (#55)

Dushan Miladinovic 1 , Thomas Cusick 2 , Anne-Maree Haynes 2 , Phillip Stricker 3 , Lisa G Horvath 4 5 , Andrew J Hoy 1
  1. The University of Sydney, The University Of Sydney, NSW, Australia
  2. Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  3. Department of Urology, St Vincent’s Private Hospital, Sydney, NSW, Australia
  4. Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
  5. Chris O’Brien Lifehouse, Camperdown, NSW, Australia

Periprostatic adipose tissue (PPAT) is a visceral adipose tissue pad surrounding the prostate. Interestingly, the thickness of the PPAT correlates with higher Gleason score, an index of histological disease grade, in prostate cancer (PCa); suggesting PPAT influences disease aggressiveness. However, little is known about the functional phenotypes of PPAT or whether the biology of PPAT is associated with PCa disease markers or patient metabolic profile. Therefore, this study assessed lipolysis of both PPAT and subcutaneous adipose tissue (SAT) in men with PCa and correlated these outcomes to patient metabolic profile and clinical parameters.

A pilot study was performed in PPAT collected from 15 men, with explants incubated in Krebs buffer alone or containing 10 nM insulin, 1 µM isoproterenol (IsoH), 10 nM isoproterenol, or 1 nM DHT with glycerol and fatty acid concentrations measured. Men with a primary Gleason score (PGS) of 4 (n=7) were more likely to have a higher BMI compared to PGS of 3 (n=8; P=0.1), concomitant with a trend towards enhanced suppression of PPAT lipolysis by insulin in PGS 4 compared to PGS 3 (P=0.13). IsoH increased lipolysis in all samples, but there was significant heterogeneity in response to other stimuli. Recently, we observed that basal and hormone-stimulated fatty acid release was similar between PPAT and SAT. Similar to the first study, all samples responded to IsoH, but heterogeneity in response to other stimuli.

In conclusion, early results suggest PPAT lipolysis may vary with disease grade, and that the responsiveness of PPAT to stimuli varies between patients. Ongoing studies aim to characterise the relationships between PPAT lipolysis, whole-body metabolic profile and PCa in larger patient cohorts.