Altogether, our extensive analysis performed in Pparαhep−/− mice has allowed us to extend the evidence for the central role of PPARα in hepatocyte fatty acid homeostasis (figure 9). PPARα is strikingly essential to many aspects of fatty acid homeostasis including degradation through oxidative pathways. Our work provides the first demonstration that hepatocyte-specific PPARα deletion impairs whole-body fatty acid homeostasis during fasting, MCD and HFD feeding as well as in ageing. These findings underscore the central role of PPARα in the clearance of dietary fatty acids and of FFA released from adipocytes, the major source of lipid accumulation in NAFLD. These data highlight the relevance of PPARα as a drug target for NAFLD treatment.
