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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #196978
Title: ALCOHOLIC HEPATOTOXICITY AND SATURATED FATS IN THE DIET: A MODULATING INFLUENCE

Author
item RONIS, MARTIN - ACNC/UAMS
item ZIPPERMAN, MICHELLE - ACNC
item BADGER, THOMAS - ACNC/UAMS

Submitted to: Alcoholism: Clinical and Experimental
Publication Type: Abstract Only
Publication Acceptance Date: 5/26/2006
Publication Date: 9/10/2006
Citation: Ronis, M.J., Zipperman, M., Badger, T.M. 2006. Alcoholic hepatotoxicity and saturated fats in the diet: a modulating influence [abstract]. Alcoholism: Clinical and Experimental Research. 30(s2):88A.

Interpretive Summary: Diet is well known to have a real impact on the development of alcohol-induced liver damage after excessive drinking. In the current study we have examined liver damage in rats after feeding diets with the same level of calories containing the same amount of alcohol but different types of fat. We have shown that saturated fats (a mix of coconut oil and beef tallow) can prevent the development of both fatty liver and inflammation after alcohol consumption compared to diets made of corn oil. The mechanism appears to involve both changes in fatty acid composition of cell membranes making them resistant to the toxic effects of oxidative stress and increased fat breakdown by oxidation in the endoplasmic reticulum and peroxysomes.

Technical Abstract: We fed male Sprague-Dawley rats (300 g) by total enteral nutrition using liquid diets with or without 12 g/kg/d ethanol (EtOH). In one control and one ethanol group, the dietary fat was corn oil at 45% total energy. In other groups, saturated fat (beef tallow: medium chain triglyceride (MCT) oil = 18:82) was substituted for corn oil at levels of 10%, 20%, and 30% of total energy, while keeping the total fat energy at 45%. After 70 days, liver pathology, serum alanine aminotransferase (ALT), biochemical markers of oxidative stress, and liver fatty acid composition were measured. In addition, expression of CYP2E1 and CYP4A and other genes involved in EtOH metabolism and fatty acid (FA) homeostasis were assessed. In rats fed the corn oil + ethanol diets, hepatotoxicity was accompanied by oxidative stress as indicated by increased lipid peroxidation and reduced GSH concentrations. As dietary saturated fat content increased, all measures of hepatic pathology and oxidative stress were progressively reduced, including steatosis (p < 0.05). Dietary saturated fat also decreased liver triglyceride, polyunsaturated free FA concentration, and total free FAs (p < 0.05). Changes in dietary fat composition did not alter ethanol metabolism or CYP2E1 induction. However, hepatic CYP4A and acyl CoA oxidase expression were highly induced in rats fed the saturated fat diets, indicating substantial increases in FA omega-hydroxylation and peroxisomal beta-oxidation. Increases in dietary saturated fat also increased liver membrane resistance to oxidative stress. These findings may have importance in the nutritional management and treatment of alcoholic liver disease.