Additionally, we questioned whether hepatocyte PPARα may also be required for the protection of the liver during early hits in steatosis such as those occurring in response to short-term exposure to a high-fat diet (HFD). Over 2 weeks of HFD, mouse liver accumulated hepatic triglycerides and cholesterol esters. Importantly, this steatosis was twice higher in Pparαhep−/− mice than in WT mice, and was further elevated in Pparα−/− mice (see online supplementary file 11). Altogether, these data suggest that hepatic PPARα is essential in hepatoprotection.