PPARα is targeted by several fibrate drugs,33 and by pan-agonists for PPAR isotypes21 that are currently in clinical trials for NASH treatment. Using Pparαhep−/− mice, we demonstrated an autonomous transcriptional response of hepatocytes to fenofibrate, indicating that fibrates’ effects on the liver gene expression are largely independent from those in extrahepatic tissues. Moreover, liver gene expression profiles markedly differed between untreated Pparα−/− and Pparαhep−/− mice, suggesting that extrahepatocytic PPARα activity substantially influenced the hepatic transcriptome.
