Not only will activated PPARα reduce the amounts of pyruvate formed, but it will also powerfully prevent the entry of pyruvate into the mitochondrial TCA cycle by strongly inducing the expression of PDK4 [36, 37]. Because PPARα simultaneously stimulates β-oxidation, it privileges FAO to provide acetyl-CoA for the generation of energy via the TCA cycle and oxidative phosphorylation (OXPHOS). As a result, pyruvate will be available for gluconeogenesis, which implies a role for PPARα in gluconeogenic regulation. Two PPREs have been identified in the promoter of PDK4 [38]. Although PDK4 expression robustly increases in response to PPARα activators and fasting, PPARα/RXRα did not bind these PPREs with high affinity in a gel-shift assay [38]. Earlier, it was already proposed that PDK4 is influenced by PPARα indirectly [39]. Because the coactivator PGC-1α is able to bind and activate the PDK4 promoter, it is believed to be involved in the upregulation of PDK4 in response to fasting [40]. The essential role of PPARα in the induction of PDK4 upon fasting was also confirmed by the absence of this response in PPARα knockout
