Effects of Prolonged Ethanol Intake: Production of Fatty Liver Despite Adequate Diets*

Abstract

To differentiate the role of ethanol per se from sequelae of dietary deficiencies in the pathogenesis of the alcoholic fatty liver, ethanol was administered with adequate diets. In studies performed under metabolic unit conditions in 5 subjects, isocaloric substitution of carbohydrate by ethanol or addition of ethanol to an adequate diet resulted in fat accumulation in the liver. This was confirmed in rats whose natural aversion for alcohol was overcome by incorporating ethanol in a liquid diet. With this new ethanol feeding technique, the spontaneous ethanol intake was almost twice as high as with conventional feeding procedures. As in man, isocaloric replacement of sucrose (36% of total calories) by ethanol produced fatty lever, with an average 8 fold hepatic triglyceride increase after 24 days. Isocaloric replacement of ethanol by fat did not produce hepatic steatosis, demonstrating that the capacity of ethanol for generating fatty liver is greater than that of fat itself. No fatty liver developed when sucrose was omitted from the control diet, indicating that the steatosis observed with ethanol was not simply due to a lack of carbohydrate calories. Rats fed the ethanol-containing diet had less total body weight gain than the controls, indicating that ethanol supports growth less well than sucrose. It is postulated that the fatty liver produced by ethanol is due to direct effects of ethanol on lipid metabolism in the liver itself, with increased lipogenesis and decreased oxidation of endogenous lipids and fat originating from the diet.