WY14643 reduced basal and glucose-stimulated PK expression in primary hepatocytes [33]. In line with these findings, clofibrate or WY14643 treatment of rats also strongly reduced PK expression [31–33] whereas this suppression did not occur in PPARα −/− mice [32]. A direct interaction of PPARα with the PK promoter could not be proven [32], and hence suppression of gene expression must involve some intermediary factors. It was proposed that ligand-activated PPARα interferes with coactivator recruitment and decreases histone H4 acetylation of PK [33]. In conflict with these observations showing suppressed glycolytic enzymes by PPARα activators, a decreased expression of glucokinase and pyruvate kinase was reported in PPARα −/− mice both in fasted and in fed conditions [20, 35].
