Hostetler et al. [60] showed that both glucose and its metabolites glucose-1-phosphate and G6P are endogenous ligands of PPARα with glucose having the highest affinity, well within the range of normal physiological levels. These metabolites are supposed to interact directly with specific amino acid residues in the PPARα ligand binding domain [60], resulting in altered PPARα secondary structure [60, 61]. After glucose binding, coactivator recruitment, DNA binding and transactivation potential of PPARα/RXRα heterodimers were increased [60], but only in the presence of activating PPARα ligands such as arachidonic acid or clofibrate. In the absence of other ligands, glucose inhibited recruitment of coactivators and therefore suppressed PPARα regulated transcription [60].
