Alcohol consumption enhances fatty acid omega-oxidation, with a greater increase in male than in female rats.
Because ethanol inhibits mitochondrial fatty acid oxidation, with substantial accumulation of fatty acids in the livers of female (but not male) rats, and induces microsomal activities, we assessed possible changes in omega-oxidation. To study this, we pair-fed 24 male and 24 female littermate rats of the same age liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 4 wk. In controls, the microsomal omega-hydroxylation of lauric acid was 28% greater in female than in male rats (p < 0.05). Ethanol feeding significantly increased this activity in both genders (p < 0.01), but the rise in male rats (89%) was significantly higher than that in female rats (24%). This activity was unaffected by the presence of ethanol in the assay. The effects of ethanol were associated with increases in the content of cytochrome P-450 4A1 (as assessed in Western blots by the reactivity against a sheep antibody against P-450 4A1), and more so in male than in female rats. Despite possible competition by ethanol with the hydroxy fatty acid oxidation to dicarboxylic acids through alcohol dehydrogenase, suberic and sebacic acids accumulated significantly in the livers of alcohol-fed male rats. These effects of ethanol and gender on omega-oxidation paralleled those on the hepatic cytosolic fatty acid-binding protein and fatty acid esterification previously reported in similarly treated rats. Dicarboxylic acid products of omega-oxidation have been incriminated as mediators of similar effects by other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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Alcohol Research and Treatment Center, Veteran Affairs Medical Center, Bronx, New York 10468.
Baraona
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Lieber
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D000818:Animals; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006900:Hydroxylation; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D005227:Fatty Acids; D007850:Lauric Acids; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A