PPARα is stimulated by various fatty acid derivatives during fasting, but specifically by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [78]. This loss of endogenous PPARα regulation in fed Cyp1b1-ko mice could arise from lower activation by these endogenous ligands or partnering co-activator proteins [79]. PPARγ, which stimulates some of these genes, provides compensatory stimuli in PPARα-null mice [44], but is highly suppressed in Cyp1b1-ko livers. However, genes that were suppressed in Cyp1b1-ko mice were fully stimulated by Wy-14,643 administration (Figure 6C), demonstrating that exogenous PPARα activation can overcome this constitutive deficiency.
