Effects of ethanol on lipid metabolism

E Baraona, C S Lieber
Journal of Lipid Research 1979, 20 (3): 289-315
Alcohol promotes accumulation of fat in the liver mainly by substitution of ethanol for fatty acids as the major hepatic fuel. The degree of lipid accumulation depends on the supply of dietary fat. Progressive alteration of the mitochondria, which occurs during chronic alcohol consumption, decreases fatty acid oxidation by interfering with citric acid cycle activity. This block is partially compensated for by increased ketone body production, which results in ketonemia. Thus, mitochondrial damage perpetuates fatty acid accumulation even in the absence of ethanol oxidation. Alcohol facilitates esterification of the accumulated fatty acids to triglycerides, phospholipids, and cholesterol esters, all of which accumulate in the liver. The accumulated lipids are disposed of in part as serum lipoprotein, resulting in moderate hyperlipemia. In some individuals with pre-existing alterations of lipid metabolism, small ethanol dose may provoke marked hyperlipemia which responds to alcohol withdrawal. Inhibition of the catabolism of cholesterol to bile salt may contribute to the hepatic accumulation and hypercholesterolemia. The capacity of lipoprotein production and hyperlipemia development increases during chronic alcohol consumption, probably as a result of the concomitant hypertrophy of the endoplasmic reticulum and Golgi apparatus. However, this compensation is relatively inefficient in ridding the liver of fat. This inefficiency may be linked to alterations of hepatic microtubules induced by ethanol or its metabolites, which interfere with the export of protein from liver to serum, promoting hepatic accumulation of proteins as well as fat. As liver injury aggravates, hyperlipemia wanes and liver steatosis is exaggerated. Derangements of serum lipids similar to those found in other types of liver disease also become apparent. The changes in serum lipids may be a sensitive indicator of the progression of liver damage in the alcoholic.

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