Selective PPAR modulator (SPPARM) model of PPARγ ligand action. Different PPARγ ligands (ligands 1, 2, and 3) bind to the ligand-binding domain of the PPARγ receptor. Each ligand receptor complex assumes a somewhat different three-dimensional conformation, leading to unique and differential interactions with cofactors, histones, other transcription factors, etc. As a result of these differential interactions, each PPARγ ligand receptor complex leads to a differential, but overlapping, pattern of gene expression. Thus, each ligand will activate, or repress, a certain set of genes, some of which are in common with other ligands, and some of which are not. Adapted from McDonnell (48).