Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor and master regulator of lipid metabolism. In the liver of rodents, PPARα is an important orchestrator of the switch from the fed to the fasted condition via activation of fatty acid catabolism by mitochondrial, microsomal, and peroxisomal β-oxidation in order to maintain energy homeostasis during fasting and to protect cells from lipid overload [1–4]. Fasting periods are characterized by increased hepatic fatty acid influx, which bears similarities with high fat feeding. Moreover, PPARα functions as a fatty acid sensor and mediates the remodeling of hepatic lipid metabolism via the induction of several genes, like fatty acid transporters, fatty acid activation genes, and key enzymes of the fatty acid oxidation (FAO) pathways [4]. Besides inducing FAO, PPARα also stimulates the synthesis of ketone bodies from fatty acids [4], which in the fasted state serve as fuel for many extrahepatic organs, such as muscle [5]. In this way, fatty acids are preferentially utilized as fuel in periods of fasting.
