Figure 2.

Selective PPARγ modulator (SPPARγM) model of PPARγ ligand action. PPARγ is a multivalent receptor whose ligand binding domain can accommodate different PPARγ ligands. Ligands 1, 2, or 3 (e.g., full agonist, partial agonist, or SPPARγM) are capable of inducing distinct receptor combinations leading to selective gene expression. Each ligand-receptor complex assumes a somewhat different three-dimensional conformation, leading to unique and differential interactions with cofactors, histones (acetylases/deacetylases), and other transcription factors. Consequently, each PPARγ ligand-receptor complex leads to a differential, but overlapping, pattern of gene expression. Thus, each ligand will activate, or repress multiple genes leading to differential overlapping expression of different sets of genes. (Adapted with permission from: J. M. Olefsky, “Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists.” Journal of Clinical Investigation, vol. 106, no. 4, pp. 467-472, 2000); H. A. Pershadsingh, “Treating the metabolic syndrome using angiotensin receptor antagonists that selectively modulate peroxisome proliferator-activated receptor-gamma.” International Journal of Biochemistry and Cellular Biology, vol. 38, nos 5-6, pp. 766-781, 2006.)