To investigate the effects of chronic ethanol administration on the mobilization and excretion of cholesterol, turnover and balance studies were carried out in baboons pair-fed cholesterolfree diets containing 50% of energy either as ethanol or as additional carbohydrate for several years. Ethanol feeding increased free cholesterol in all plasma lipoprotein fractions, and esterified cholesterol in very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein (HDL). The major increase occurred in HDL, mainly as esterified cholesterol. The latter was associated with decreased transfer of esterified cholesterol from HDL to low density lipoprotein. By contrast, the smaller increase in HDL-free cholesterol was associated with increased turnover in the plasma, increased splanchnic uptake, and increased fecal excretion of plasma cholesterol, mainly as neutral steroids. Cholesterol extraction predominated over release in the splanchnic vascular bed, suggesting that the excess of cholesterol excreted in the feces originated in extrasplanchnic tissues. Thus, these findings indicate that alcohol consumption favors mobilization of tissue free cholesterol for hepatic removal and excretion. By contrast the increase in HDL-cholesterol (mainly esterified) appears to be a poor indicator of cholesterol mobilization.

1. Sixteen obese @/fa) Zucker rats, sixteen lean (Fa/-) Zucker rats and sixteen Wistar rats, all male rats aged 7-8 weeks, were given either a control (C) diet containing no ethanol or an ethanol (E) diet in which 36% of the energy was supplied by ethanol, for a period of 4 weeks.2. The activities of glucose-6-phosphate dehydrogenase (EC 1 . 1 . I .49), glucose-6-phosphatase (EC 3.1 .3.9) and glycerol kinase (EC 2 . 7 . 1 .30) and the glycogen content in the livers of obese (fa/fa) rats were lower in animals given diet E than in those given diet C. As a result, hepatic lipogenesis and fatty degeneration of the liver were reduced in obese (fa/fa) rats given diet E.Chronic alcohol intoxication of the genetically-obese (falfa) Zucker rat does not affect the degree of obesity or its hyperlipidaemia. Paradoxically, however, such intoxication results in less fatty degeneration of the liver than is found in control animals (Karsenty et al. 1985). To improve our understanding of this latter phenomenon, we have studied hepatic lipogenesis, which is one factor in the development of fatty infiltration of the liver. M A T E R I A L S A N D METHODS Animal trialsSixteen Wistar rats (CESAL-Vigneul-sous-MontmCdy) and sixteen obese (fu/fa) and sixteen non-obese (Fa/-) Zucker rats (CNRS-OrlCans-la-Source), all male rats aged 7-8 weeks, were divided into six groups of eight rats. Each group was allowed free access to a diet containing ethanol (diet E; 36% of total energy from ethanol) or a control, alcohol-free diet (diet C). Details of diet composition and animal housing have been described elsewhere (Karsenty et a2. 1985).At the end of the 4th week, blood samples were obtained by abdominal aortic puncture for plasma enzyme activity assays. One rat from each group was killed daily between 08.30 and 10.30 hours, changing the order each day, and the liver was rapidly removed, weighed and homogenized (Ultraturrax Polytron Mixer, Type PT 10-35). Two homogenates were prepared: one in 0.66 mM-EDTA-saline (9 g sodium chloride/l) buffer (Schmidt et al. 1958) for the estimation of glucose-6-phosphate dehydrogenase activity and glycogen; the other in 5 mM-Tris, 250 mM-saccharose buffer, pH 7.4 (Beaufay et al. 1974), for measurement of liver protein and the other enzyme activities. AssaysHepatic glycogen was extracted according to Pfleiderer (1963) and the resulting glucose assayed using Trinder's (1969) method.For reprints.

1. The effect of chronic alcohol intoxication on metabolic disturbances and fatty infiltration and degeneration was studied in genetically obese, hyperlipoproteinaemic, fa/fa Zucker rats.2. Sixteen obese Zucker (fa/fa) rats, sixteen lean Zucker rats (Fa/-) and sixteen Wistar rats, all male rats aged 7-8 weeks, weregiveneitheracontrol (C)diet (13% ofenergyfromprotein, 37% fromfat, 50% fromcarbohydrate) or an ethanol (E) diet (13% of energy from protein, 37% from fat, 14% from carbohydrate, 36% from ethanol) for 4 weeks.3. Thefalfa rats given diet E consumed more energy than those given diet C, but after 4 weeks the weight gains and degrees of obesity were similar for both groups. With both diets, the developed hyperlipidaemia could be explained by the hyperinsulinaemia. Both hypertriglyceridaemia and hypercholesterolaemia were lower in fa/fa rats eating diet E than in those given diet C . Fatty infiltration of the liver, as assessed by hepatic triacylglycerol and cholesterol contents, was observed with both diets, but for fa/fa rats it was less extreme in those given diet E.Chronic alcohol intoxication in rats leads to liver steatosis (fatty infiltration and degeneration of the liver) (Lieber et al. 1965; De Carli & Lieber, 1967; Baraona & Lieber, 1979;Reitz, 1979) with (Redgrave & Martin, 1977;Lederer et al. 1978) or without hyperlipoproteinaemia (Hirayama et al. 1979). As the genetically obesefalfa Zucker rat has both these metabolic disorders, we have studied this species to determine if these conditions are exacerbated by chronic alcohol intoxication. MATERIALS A N D METHODS AnimalsForty-eight male rats were used : sixteen Wistar rats (CESAL, Vigneul-sous-Montmedy), sixteen obese (fa/'a) and sixteen lean (Fa/-) Zucker rats (CNRS, Orleans-la-Source). They were housed individually in randomly assigned cages and allowed to adapt over a 2-week period, during which they were allowed free access to a standard diet (UAR no. A 04, Villemoisson-sur-Orge) containing (g/kg) : protein 170, carbohydrate 587, lipid 30. At 7-8 weeks of age, equal numbers of each strain were randomly assigned to a control (C) or an ethanol-containing (E) diet, and they were allowed free access to food and tap water for a 4-week experimental period. The rats were weighed on arrival and at weekly intervals thereafter. DietsThe compositions of diets C and E are given in Table 1. The diets were given in a semi-liquid form to simplify ethanol incorporation and preserve a homogenous appearance. The proportion of ethanol in diet E was progressively increased at the expense of maize starch over the first 5 d. Amounts of ethanol given (g/kg dry diet) were 180 for the first 2 d, 240