Importantly, there are clear differences in PPARα biology between mice and humans. It was long thought that in comparison with mouse liver, human liver contains 10-fold lower levels of PPARα mRNA [12], but recent investigations indicated that both species contain comparable levels [13] which may fluctuate throughout the day and according to feeding status. Although the induction of mitochondrial FAO and lipid-lowering effects are universal for PPARα ligands, they do not induce peroxisome proliferation or tumor development in the liver of species other than rodents [14, 15]. Using primary mouse and human hepatocytes, it was demonstrated that besides the common regulation of lipid metabolism, PPARα ligands induce a divergent set of genes in both species [13]. Notably, changes in carbohydrate gene expression were only observed in mouse hepatocytes.
