MCD diet is widely used for preclinical NASH studies. However, it has many limitations, including the important weight loss that occurs in mice fed such diet. Therefore, we also tested the role of hepatocyte PPARα in lipid homeostasis in response to a short-term HFD feeding, which is sufficient to initiate early neutral lipid accumulation that may promote NAFLD. Pparαhep−/− mice showed marked increase in hepatic steatosis in response to 2 weeks of HFD feeding (see online supplementary file 11) suggesting that hepatocyte PPARα plays a dual role in exogenous (dietary) as well as in endogenous (released from adipocyte lipolysis) fatty acid homeostasis.
