Fig. 7.

Scheme illustrating lipid metabolite alterations, related pathways, and implicated genes in human PPAT and PCa cell lines. In “aggressive” PPAT adipocytes, lower concentrations of 13-oxoODE, an endogenous ligand for PPARG, may provoke transcriptional upregulation of the proinflammatory cytokines IL-6, IL-1B, and TNFα. De novo lipogenesis is also reduced, as the expression levels of ACACA and FASN are downregulated. The resulting process translated to reduced concentrations of palmitic acid and its saturated FA intermediates (produced by elongation process): stearic acid, arachidic acid, behenic acid, and lignoceric acid. FAs from TG lipolysis can also be contemplated as another FA source. Reduced expression levels of lipase LIPE and the mitochondrial transporter CPT1A may indicate suppressed FA lipolysis. An increase in the expression of the FABP4 lipid transporter gene points to active FA mobilization to PCa cells. PCa cells can take-up the FA released from PPAT adipocytes followed by an increased expression of lipid transporter genes (CD36, FATP5), fuelling cellular de novo lipogenesis and lipolysis. An active proinflammatory state is also observed in PCa cells. Abbreviations: 13-HODE, 13 hydroxy-octadecadienoic acid; 13-oxoODE, 13-oxo-octadecadienoic; PPARG, peroxisome proliferator-activated receptor gamma; IL-6, interleukin 6; IL-1B, interleukin 1 B; TNFα, tumor necrosis factor alpha; FASN, fatty acid synthase; SREBP-1, sterol regulatory element binding transcription factor 1; ACACA, acetyl-CoA; CPT1A, carboxylase alpha; Carnitine Palmitoyl transferase 1A; LIPE, hormone-sensitive lipase; MG, monoglyceride; DG, diglyceride; TG, triglyceride; FABP4, fatty acid binding protein 4; FA, fatty acid; PNPLA2, patatin-like phospholipase domain containing 2; CD36, CD36 molecule; LPL, lipoprotein lipase