Pathogenesis of postprandial hyperlipemia in rats fed ethanol-containing diets.

To study the mechanism of the increase in serum lipoproteins which occurs in rats fed alcohol chronically, and especially to assess the role of the intestine, the effects of acute and chronic ethanol administration on lymph and plasma lipids were compared in rats with and without intestinal lymph fistulae. In rats not previously given alcohol, the administration of one dose of a diet containing ethanol (3 g/kg) produced a significant increase in lymph flow, lipid output, and incorporation of dietary fat into lymph lipids when compared with the effects of a control diet containing isocaloric carbohydrate. However, no hyperlipemia developed after ethanol. By contrast, previous feeding of ethanol for several weeks modified the acute effects of ethanol on both lymph and serum lipids. Compared with control animals pair-fed with isocaloric carbohydrate-containing diets, rats which had been fed a diet with 36% of total calories as ethanol for 3-4 wk developed postprandial hyperlipemia when given a single dose of the ethanol-containing or even the ethanol-free diet. This was associated with an increased incorporation of labeled dietary fat and of intravenously injected [(3)H]lysine into plasma lipoproteins of d < 1.006. However, postprandial lymph flow and lipid output were not higher in rats fed alcohol chronically than in their pair-fed controls. Moreover, when rats with lymph fistulae were given intravenous (i.v.) infusions of lymph lipids (to substitute for the diverted intestinal lymph), the ethanol-fed animals still developed hyperlipemia. Incorporation of i.v. lysine into d < 1.006 plasma lipoproteins also remained significantly increased. Thus, under these conditions, alcoholic hyperlipemia does not result from changes in intestinal lymph lipids. Two main factors appear to be involved; the acute effects of ethanol on hepatic lipid metabolism and the development of an increased capacity for lipoprotein synthesis during chronic ethanol feeding. The latter most likely occurs in the liver and it is postulated that it is linked to the associated changes in the hepatic endoplasmic reticulum.