Lastly, we questioned the long-term consequences of hepatocyte-specific Pparα deletion during ageing. More specifically, since PPARα is broadly expressed in metabolic tissues, we aimed at clarifying whether the steatosis that develops in aged whole-body Pparα−/− mice is due to the hepatocytic defect in PPARα activity. WT, Pparαhep−/− and Pparα−/− mice were fed a standard diet over 1 year. Pparα−/− mice, but not Pparαhep−/− mice, grew overweight with ageing (figure 8A–C). Both Pparαhep−/− and Pparα−/− mice showed spontaneous centrilobular steatosis (figure 8D), elevated hepatic triglycerides and hepatic cholesterol esters (figure 8E), as well as hypercholesterolaemia (see figure 8F online supplementary file 12) without hyperglycaemia (figure 8G). Overall, hepatocyte-specific PPARα deficiency was sufficient to induce spontaneous steatosis and disrupt whole-body fatty acid as well as cholesterol homeostasis, but did not affect weight gain and diabetes during ageing.
