retinol-oleate and Liver-Diseases--Alcoholic

Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body's retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minor RE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease.

Topics: Acyltransferases; Adipose Tissue, White; Alcohol Drinking; Animals; Diacylglycerol O-Acyltransferase; Diterpenes; Esterification; Esters; Glycerol-3-Phosphate O-Acyltransferase; Hydrolysis; Liver; Liver Diseases, Alcoholic; Lung; Male; Mice; Mice, Inbred C57BL; Phosphatidylcholines; Retinyl Esters; Vitamin A

Liver retinoid levels and the retinyl esters were examined in liver biopsy specimens from 70 patients with alcoholic and nonalcoholic liver diseases. There was a wide variation in the liver retinoid levels. The liver retinoid level was statistically significantly lower in 15 patients with alcoholic liver disease and a depressed Normotest (NT) value of less than 65% compared with patients with alcoholic liver disease and a normal NT value of greater than 65% (P less than 0.01). The mean serum retinol level in patients with alcoholic cirrhosis was 0.68 +/- 0.38 mumol/l compared with 1.99 +/- 1.14 mumol/l in patients with alcoholic fatty liver (P less than 0.03). The relative amount of retinyl oleate was increased in the alcoholic fatty liver compared with the nonalcoholic fatty liver (P less than 0.001).

Topics: Adult; Aged; Diterpenes; Ethanol; Fatty Liver; Fatty Liver, Alcoholic; Female; Humans; Liver; Liver Diseases; Liver Diseases, Alcoholic; Male; Middle Aged; Retinoids; Retinol-Binding Proteins; Retinyl Esters; Vitamin A