The finding that PPARα activation appears to have a detrimental role in hepatic steatosis may go some way to explaining the lack of success in trying to exploit PPARα as a therapeutic target in NAFLD treatment.49,52,53 However, if one considers that the function of the complement of genes regulated by PPARα is largely associated with fatty acid metabolism, de novo lipogenesis and lipid transport it becomes clear that a PPARα naive system would have a reduced capacity for TAG accumulation. This evidence concerns the gene PPARA and fatty liver disease.