Hepatic fatty acid metabolism is regulated by the inter-play between a set of nuclear receptors. These include peroxisome proliferator-activated receptors gamma and alpha (PPARγ, PPARα, respectively), constitutive androstane receptor and hepatocyte nuclear factor 4 alpha (HNF4α), which are activated by fatty acids or their derivatives, and pregnane X receptor, liver X receptor and farnesyl X receptor, which are activated by cholesterol derivatives [13–14]. Hepatic PPARs play a key role in maintaining energy homeostasis during periods of fasting, including the regulation of the storage of fatty acids as triglyceride droplets [15]. Activation results in increased fatty acid uptake and oxidation, lipogenesis and gluconeogenesis/glycolysis. The microsomal oxidase, stearoyl CoA desaturase 1 (Scd1), which is particularly sensitive to suppression by hypothalamic leptin signaling, enhances this storage while decreasing mitochondrial oxidation [16–17].
