The observation that increased PPARalpha/PPARgamma ratio counters hepatic lipogenesis, even with a lack of effect upon SREBP-1c expression, creates new perspectives aiming to unravel pathways by which PPARalpha can protect the liver against lipogenesis induced by PPARgamma overexpression as well as the precise mechanisms that underlie SREBP-1c and PPARgamma interaction in the development of NAFLD. This evidence concerns the gene PPARA and metabolic dysfunction-associated steatotic liver disease.