Finally, ethanol and retinoid metabolisms are widely interconnected [124]. Liver from alcoholics shows a marked depletion of Vitamin A that correlates with the activation of stellate cells, their loss of lipid droplets and differentiation in myofibroblast-like cells. The role of nuclear receptors in stellate cells activation is widely studied and it is reported elsewhere in this paper. Key enzymes in ethanol metabolism may act also on retinol pathway [125]. Enhanced activities of ADH, ALDH, and CYP2E1 in alcoholics may account for the observed reduction of Vitamin A in liver cells. Even if retinol it is not their supposed primary substrate it is well known that ADHs and ALDHs may catalyze the conversion of Vitamin A to retinoic acid accelerating retinol metabolism; furthermore alcohol induction of cytochrome CYP2E1 determines a higher rate of Vitamin A catabolism in polar metabolites in the liver. Ethanol may also increase retinol mobilization from liver increasing hydrolization of retinyl esters [126–128]. Alcohol-induced effects on retinol-regulated genes are further increased by RXR downregulation observed in alcohol-fed animals. This establishes a complex regulatory mechanism between RXR, retinol metabolism, and ethanol that is deregulated during heavy ethanol consumption.
