Figure 10.

PPAR signaling pathways influence metabolic capacity, growth, and survival. There are three subtypes of peroxisome proliferator-activated receptor proteins (PPARs). PPARs are nuclear hormone receptors that are activated primarily by eicosanoids, unsaturated fatty acids, NSAIDS, and retinoic acid. Their activation status is also influenced by cAMP second messenger cascades and MAP kinase signaling activated by G-protein-coupled receptors (GPCRs) and growth factor receptor (GFR)-activated signaling. Upon heterodimerization with retinoic acid receptors (RXRs) and association with hydrophobic ligands, PPARs translocate to the nucleus. There, the complexes activate transcription of metabolic genes. PPARα agonism disrupts HIF1α-mediated transcriptional activation of PKM2, thereby reducing glycolysis; PPARα has also been implicated in tumor suppression and apoptotic initiation through various signaling pathways. PPARγ enhances mitochondrial biogenesis, fatty acid oxidation, and insulin-mediated glucose transport into cells; PPARγ is also anti-inflammatory, preventing the activation of STAT1, AP1, and NFκB. In many contexts, non-ligand-activation of PPAR induces transcriptional repression. The effects of PPARβ signaling in glioma are not known.