Excessive alcohol consumption is known to result in fatty liver, or steatosis. A high-fat, low-carbohydrate diet also results in fatty liver. Furthermore, fatty liver is known to precede cirrhosis in both animals and humans, and cirrhosis precedes primary hepatocellular carcinoma in humans. A series of studies was first undertaken to determine whether exercise and/or certain dietary manipulations could affect fatty liver. Long-Evans rats were given either a high-fat, low-carbohydrate or a high-carbohydrate, low-fat version of liquid diet with or without alcohol. Livers were analyzed for fat and measures of carbohydrate metabolism in liver and plasma were taken, as well as blood glucose alcohol concentrations. Next, added exercise (run wheel), caffeine, antioxidants such as Vitamin E, diphenyl-para-phenylene diamine (DPPD), and selenium were examined as were the dietary additives cranberry powder and soy protein. Finally, based on ambiguous results involving each agent separately, caffeine and DPPD were combined. Following the conclusion of rat studies, C57BL6 mice were given a modified version of the Leiber-deCarli liquid diet with alcohol. The calorie manipulation described above was repeated in mice to determine whether alcohol-induced fatty liver would be exacerbated in the presence of a high-fat diet. Subsequently, the dietary additives Vitamin E, DPPD and Trolox were added. Striatum was taken for HPLC, and livers were taken for liver fat analysis and malondialdehyde (MDA) assay (as a measure of oxidative stress) respectively. Finally, an experiment was undertaken to determine a time course for withdrawal seizures in mice.
In rats, differences in liver glycogen did not account for differences in liver fat. Exercise and caffeine both resulted in significant changes in weight gain, and while combined they appeared to reduce alcohol-induced fatty liver, the effect was not significant. Separately, no protective properties of either exercise or caffeine were observed. Vitamin E and selenium were found to exacerbate alcohol-induced fatty liver, while DPPD did not. Neither cranberry powder nor soy protein affected alcohol-induced fatty liver. DPPD combined with caffeine reduced alcohol-induced fatty liver significantly (p<0.05).
Adult mice were able to tolerate 4.5% ethanol in a high-fat liquid diet. The high-fat diet resulted in liver fat values significantly higher than high-carbohydrate when combined with alcohol. Vitamin E appeared to exacerbate fatty liver in mice, but differences were not significant. There were significant differences in oxidative stress; Vitamin E and Trolox reduced MDA significantly over diet plus alcohol alone. All animals experienced withdrawal seizures between 3 and 5 hours after removal of alcohol. There were significant differences in serotonin turnover (5HIAA/5HT) in animals fed a high-fat diet without alcohol vs. chow controls.Ph.D.Includes bibliographical references (p. 52-60)by Bonnie Nola
