EFFECTS OF ETHANOL FEEDING ON LIVER, KIDNEY AND JEJUNAL MEMBRANES OF MICROPIGS

The micropig model of chronic alcoholism was used to study the relatio nship of lipid composition and physical properties in three different tissue membranes from the same animals. Ethanol feeding reduced membra ne anisotropy, as measured with the diphenylhexatriene probe, in liver plasma and kidney brush-border membranes but not in jejunal brush-bor der membranes. Preincubation with ethanol reduced anisotropy in each o f the three control membranes, whereas all three membranes from the et hanol-fed group were relatively tolerant to the acute effect of ethano l. In liver and kidney membranes, ethanol feeding increased levels of linoleic (18:2 omega 6) acid and decreased levels of arachidonic (20:4 omega 6) and docosahexaenoic (22:6 omega 3) acids and their specific double-bond positions, consistent with reduced activities of Delta 6 a nd Delta 5 fatty acid desaturases. In liver and kidney membranes, anis otropy parameters and the acute effect of ethanol correlated inversely with levels of linoleic acid and directly with levels of arachidonic and docosahexaenoic acids and their specific double bonds. Levels of d ocosahexaenoic acid correlated with the acute effect of ethanol in all three membranes. Phospholipid fatty acid profiles were similar in jej unal brush-border membranes and terminal bile samples, suggesting that the effects of ethanol on jejunal fatty acids and physical properties are modulated by intraluminal biliary phospholipids. The effect of et hanol on anisotropy could not be attributed to changes in membrane cho lesterol/phospholipid ratios. These studies affirm the value of this n ew animal model of chronic alcoholism and provide comprehensive eviden ce for the central role of fatty acid desaturation in the membrane-ass ociated effects of ethanol exposure.