Ethanol-induced hepatic fibrosis in the rat: role of the amount of dietary fat.

We have made a comparison between groups of rats fed ethanol and a diet that received intragastric infusion of ethanol continuously for prolonged periods varying only in the amount of fat in the diet (percentage of total calories as fat was 5, 25, and 35%). A fourth group of rats fed high fat (32% of calories) and a diet marginal in protein, vitamins and minerals was also studied. Control rats were pair-fed dextrose in isocaloric amounts. For rats fed diets containing 5, 25, 32, and 35% fat, the average blood alcohol levels achieved were 216, 224, 266 and 353 mg/100 ml, respectively. Average weight gains of the ethanol fed rats were: 15.4, 19.6, 14.7, and 14.9 g/week, respectively. Serum alanine aminotransferase (ALT) levels of the ethanol-fed rats averaged 123, 292, 144, and 213 units/liter, respectively. ALT levels in pair-fed controls for the rats fed 32% fat averaged 62 and those of chow-fed controls averaged 49 units/liter. Comparison of liver biopsy-semiquantified morphological findings revealed an increased 3-4+ fatty change in the ethanol-fed rats also fed the high fat rats. Moreover, fibrosis was only observed centrilobularly in rats fed diets with varying fat content (5, 25, 32, or 35% of calories): 0/16, 10/17, 4/6, and 3/7 rats, respectively, over a 5-mon period of feeding. Electron microscopy showed that ito cells predominated in the scarred areas. The mechanism for the centrilobular necrosis-fibrosis was investigated in rats given a diet of ethanol plus 32% fat diet by measuring the level of adenine nucleotide in repeated liver biopsies in five pair of rats.(ABSTRACT TRUNCATED AT 250 WORDS)