Purpose Excess visceral fat and altered lipid metabolism are both associated with prostate cancer progression. Our aim was to determine if a weight loss lifestyle intervention using diet and exercise changed the intake of dietary fat and nutrients, the fatty acid composition and signaling pathways of periprostatic adipose tissue (PPAT), and the sphingolipid signature in the blood in men with prostate cancer.

Materials and Methods Forty men scheduled for radical prostatectomy (RP) were randomized into intervention (n=20) or active control (n=20) arms in a phase II trial. Participants in the intervention adhered to a lifestyle intervention using diet and exercise for 4-16 weeks before and 6-months after RP. Participants in the active control arm were given standard of care and standardized educational materials. Blood samples, dietary information, and health metrics of participants were collected at three time points: baseline (4-16 weeks prior to RP), 1 week prior to RP, 6 months after RP. PPAT biopsies were collected at the time of RP. Fatty acid analysis of PPAT was performed using flame-ionization gas chromatography. RNA from third passage adipose stromal cells (ASCs) were isolated using a RNeasy kit (Qiagen). RNA samples were analyzed using nCounter® PanCancer Immune Panel (NanoString). Sphingolipids were analyzed in plasma via Xevo GS-X2 quadrupole time-of-flight mass spectrometers using a 2D column configuration.

Results The weight management program produced clinically significant weight loss in the intervention group compared to the control arm, with 5.5% weight loss from baseline to surgery. Dietary intake of myristic acid, palmitic acid, margaric acid, stearic acid, linoleic acid, arachidic acid, and linolelaidic acid significantly decreased in the intervention group from baseline to pre-surgery; between arm changes were significant. Oleic acid consumption significantly increased in the intervention group; between arm changes were significant. ASC transcriptomic analysis revealed lower gene expression of COLEC12 and higher expression of IL-17F, and biological mapping of transcriptome data using Ingenuity Pathway Analysis predicted inhibition of leptin and IL-6 signaling in the intervention group. The plasma sphingolipid signature significantly decreased in the intervention group and did not change in the control group.

Conclusions Our study demonstrated significant changes in the intake of dietary fatty acids which did not correlate with effects on the composition of the PPAT. Clinically significant weight loss produced transcriptomic changes in the PPAT, with downregulation of pathways associated with PCa progression. The improved plasma sphingolipid signature in the intervention suggests favorable changes in lipid metabolism protective against prostate cancer progression.