Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders

Figure 2

Signaling pathways activating PPAR and regulating the biological effects of PPAR in different organs. PPAR activity can be regulated by the direct binding of small lipophilic ligands. Ligand-unbound PPAR in the cytosol is associated with chaperons, and the association changes the conformation of PPAR that allows for high-affinity binding to the ligand. Ligand-bound PPAR forms a heterodimer with RXR, and the PPAR-RXR heterodimer constructs the transcriptional machinery through the recruitment of coregulators. The transcriptional machinery regulates gene expression by binding to specific DNA sequence elements, termed PPAR response elements (PPRE). PPARα is strongly expressed in the liver, heart, and blood vessels, and regulates the expressions of genes related to lipid metabolism and inflammation control. PPARγ exerts its effects on insulin sensitivity and glucose homeostasis in adipocytes and skeletal muscles. PPARδ is expressed ubiquitously, and controls the expressions of genes that are involved in glucose and lipid metabolism. FA: fatty acid; HDL: high-density lipoprotein; VDL: very low-density lipoprotein; ABCA1: ATP-binding cassette transporter A1; UCP: uncoupling protein; TG: triglyceride.