PPARs can be activated by many natural or synthetic PPAR ligands. Upon ligand binding, PPARs form heterodimers with the retinoid X receptor (RXR), which then promotes the recruitment of coactivators and the release of corepressors. The coactivators bind to the PPAR/RXR heterodimer at the promoter regions of downstream genes, regulating the transcription of these genes, which are primarily involved in lipid and glucose metabolism, inflammation, and cancer, among other processes. Additionally, PPARs can negatively regulate gene expression without binding to DNA, for example, by directly inhibiting the activity of other transcription factors, such as competing to suppress pathways like NF-κB, AP-1, and JAK-STAT during inflammatory responses, thereby acting to suppress inflammation.