Peroxisome proliferator-activated receptor and retinoic x receptor in alcoholic liver disease.
A growing number of new studies demonstrate that nuclear receptors are involved in the development of alcoholic liver disease (ALD). Ethanol metabolism and RXR/PPAR functions are tightly interconnected in the liver. Several ethanol metabolizing enzymes are potently regulated by RXR and PPARalpha after alcohol consumption. The increased ethanol metabolism, in turn, leads to alteration of the redox balance of the cells and impairment of RXR/PPAR functions by direct and indirect effects of acetaldehyde, resulting in deranged lipid metabolism, oxidative stress, and release of proinflammatory cytokines. The use of animal models played a crucial role in understanding the molecular mechanisms of ALD. In this paper we summarize the reciprocal interactions between ethanol metabolism and RXR/PPAR functions. In conclusion, RXR and PPAR play a central role in the onset and perpetuation of the mechanisms underling all steps of the clinical progression in ALD.
Mello
Tommaso
T
Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50134 Firenze, Italy.
Polvani
Simone
S
Galli
Andrea
A