DIETARY FISH-OIL POTENTIATES BILE ACID-INDUCED CHOLESTEROL SECRETION INTO BILE IN RATS

Recently we demonstrated that dietary fish oil (FO) causes changes in intrahepatic cholesterol transport and hyper secretion of cholesterol into bile in rats V. Clin. Invest. 88: 943-951, 1991). We have now inv estigated in more detail the relationship between cholesterol and bile acid secretion in rats with chronic bile diversion fed purified diets supplemented (9% wt/wt) with either FO or corn oil(CO) for 2 weeks. E ffects of FO on biliary cholesterol secretion(+ 400% as compared to CO after 14 days) were much more pronounced than previously observed in rats with intact enterohepatic circulation (+50%). Biliary bile acid ( +30%) and phospholipid (+120%) secretion were increased to a much less er extent than that of cholesterol resulting in the formation of bile supersaturated with cholesterol. The biliary cholesterol/bile acid mol ar ratio was 0.069 and 0.032 in FO- and CO-fed rats, respectively, at noon of day 14. This ratio increased to 0.108 in FO-fed rats at midnig ht, when bile acid output was maximal, but remained unchanged in CO-fe d rats during the day-night cycle. Intravenous administration of tauro chenodeoxycholic acid (15 mu mol/kg) resulted in a 2-fold increase in bile acid output and a simultaneous 1.6-fold stimulation of cholestero l secretion in both groups, implying that administration of the bile a cid induced the secretion of 2-3 times as much cholesterol in FO- than in CO-fed rats. Likewise, administration of bilirubin ditaurate (30 m u mol/kg), an inhibitor of bile acid-induced biliary lipid secretion, reduced cholesterol output in both groups by about 50% while bile acid output remained unchanged. It is concluded that, in rats, dietary fis h oil increases the disposition of cholesterol into bile by potentiati ng bile acid-dependent cholesterol secretion, presumably by facilitati ng the recruitment of bile-destined cholesterol.