Combating Atherosclerosis With LXRα And PPARα Agonists: Is Rational Multitargeted Polypharmacy the Future of Therapeutics in Complex Diseases?

The complex interactions between the LXRα and PPARα intracellular signaling pathways and their overall effects on cholesterol and triglyceride metabolism. Activation of PPARα induces LXRα , while several PPARα ligands (some fatty acids and the acidic forms of fibrates) suppress LXRα transcriptional activity. LXRα and PPARα may also suppress each other’s transcriptional activity by competing for their common heterodimer partner RXR, while LXRα regulates its own expression in an ultrashort positive feedback loop. Chol, cholesterol; LXRα, liver X receptor α; PPARα, peroxisome proliferators activator receptor α; RXR, retinoid X receptor; TG, triglycerides.