The use of alcohol-fed rodents played a crucial role in understanding the molecular mechanisms of ALD. However, important differences exist in the regulation of the oxidative metabolism between rodents and humans. In fact, while in rodents the need for increased oxidative metabolism induces peroxisome proliferation, humans exclusively respond by increased mitochondrial β-oxidation. Moreover, the levels of PPARα receptor are markedly lower in humans than in rodents, and this may be even more striking during alcohol abuse. PPAR and RXR KO mouse models highlighted the reciprocal regulation of PPAR, RXR and ethanol in alcoholic liver disease. In conclusion, RXR, and PPAR play a central role in the onset and perpetuation of the mechanisms underlying all steps of the clinical progression in alcoholic liver disease.
