Previous studies have shown that Pparα−/− mice show a significant alteration of systemic lipid metabolism that leads to hepatic steatosis in ageing mice. Since PPARα is active in skeletal muscles,23 adipose tissues,24 25 intestines,26 kidneys27 and heart,28 which all contribute to fatty acid homeostasis, it is impossible to determine whether the spontaneous steatosis that occurs in ageing Pparα−/− mice originates from a defect in the hepatocytic PPARα activity. This led us to investigate ageing-related differences between Pparα−/− and Pparαhep−/− mice. During ageing, Pparα−/− mice became overweight and developed steatosis, while Pparαhep−/− mice only suffered steatosis. Therefore, neither obesity nor hyperglycaemia, which are both known to promote NAFLD,15 16 is responsible for the steatosis observed in mice with hepatocyte-specific PPARα deletion.
