Idebenone and coenzyme Q are novel PPARα/γ ligands, with potential for treatment of fatty liver diseases.

Current peroxisome proliferator-activated receptor (PPAR)-targeted drugs, such as the PPARγ-directed diabetes drug rosiglitazone, are associated with undesirable side effects due to robust agonist activity in non-target tissues. To find new PPAR ligands with fewer toxic effects, we generated transgenic zebrafish that can be screened in high throughput for new tissue-selective PPAR partial agonists. A structural analog of coenzyme Q (idebenone) that elicits spatially restricted partial agonist activity for both PPARα and PPARγ was identified.