[The Perspective of PPAR Dual/Pan Agonists as Therapeutic Drugs against NAFLD].

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic fatty liver (NAFL) and a more advanced condition with inflammation/fibrosis, nonalcoholic steatohepatitis (NASH), is emerging as one of the most prevalent chronic diseases associated with the worldwide expansion of the obese population; however, there are currently only symptomatic therapy but no cure. Among multiple candidate drugs that have been developed and tried in clinical trials against NAFLD/NASH, peroxisome proliferator-activated receptor (PPAR) dual/pan agonists continue to be the most expected ones. This review summarizes the current condition of several PPAR agonists that were and are in clinical trials against NAFLD/NASH. In addition, we recently expanded structural information about PPARα/δ/γ-ligand interactions by X-ray crystallography and executed comparative functional analyses of PPARα/δ/γ activation by those ligands; based on those knowledge, we propose the reevaluation or repositioning of currently approved PPAR agonists, saroglitazar, bezafibrate, and pemafibrate, for the treatment of NAFLD/NASH.