Furthermore, both Pparα−/− and Pparαhep−/− ageing mice were hypercholesterolaemic. This is likely due to the dysregulation of apolipoproteins gene expression as well as cholesterol transport (Abcg8) as revealed in microarray analysis (see online supplementary file 12A). It is also possible that the cholesterol biosynthesis pathway driven by SREBP-2 may be dysregulated in the absence of PPARα since some of the SREBP-2 genes are elevated in Pparα−/− and/or in Pparαhep−/− mice (see online supplementary file 12B). Therefore, this suggests that drugs that activate hepatocytic PPARα will likely influence whole-body fatty acid and cholesterol homeostasis.
