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PPAR Research
Volume 2009 (2009), Article ID 748174, 11 pages
http://dx.doi.org/10.1155/2009/748174
Review Article

Peroxisome Proliferator-Activated Receptor and Retinoic X Receptor in Alcoholic Liver Disease

1Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50134 Firenze, Italy
2FiorGen Farmacogenomic Foundation, Via Luigi Sacconi 6, 50019 Firenze, Italy

Received 31 January 2009; Revised 19 May 2009; Accepted 13 July 2009

Academic Editor: James P. Hardwick

Copyright © 2009 Tommaso Mello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 PPAR 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.