PPAR signaling pathway

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are activated by fatty acids and their derivatives. The peroxisome proliferator-activated receptors (PPARs) belong to the ligand-inducible nuclear hormone receptor superfamily including three major members: PPARα (also called NR1C1), PPARβ/δ (also called NR1C2), and PPARγ (also called NR1C3). The three subtypes show different expression patterns in vertebrates. Despite several similarities, each PPAR isoform shows specific functions likely due to different biochemical properties, variable tissue distribution, and differential responses to different ligands. Each of them is encoded in a separate gene and binds fatty acids and eicosanoids. PPARα plays a role in the clearance of circulating or cellular lipids via the regulation of gene expression involved in lipid metabolism in liver and skeletal muscle. PPARβ/δ is involved in lipid oxidation and cell proliferation. PPARγ promotes adipocyte differentiation to enhance blood glucose uptake. PPAR transcriptional activity can be modulated through a nongenomic cross talk with phosphatases and kinases, including ERK1/2, p38-MAPK, PKA, PKC, AMPK, and GSK3. PPARs can form heterodimers with retinoid X receptor (RXR) modulating the expression of genes involved in lipid metabolism, adipogenesis, maintenance of metabolic homeostasis, and inflammation and inducing also anticancer effects in a variety of human tumors.

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