title: Dietary fish oil potentiates bile acid-induced cholesterol secretion into bile in rats.
abstract: Recently we demonstrated that dietary fish oil (FO) causes changes in intrahepatic cholesterol transport and hypersecretion of cholesterol into bile in rats (J. Clin. Invest. 88: 943-951, 1991). We have now investigated 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. Effects 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 lesser extent than that of cholesterol resulting in the formation of bile supersaturated with cholesterol. The biliary cholesterol/bile acid molar 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 midnight, when bile acid output was maximal, but remained unchanged in CO-fed rats during the day-night cycle. Intravenous administration of taurochenodeoxycholic acid (15 mumol/kg) resulted in a 2-fold increase in bile acid output and a simultaneous 1.6-fold stimulation of cholesterol secretion in both groups, implying that administration of the bile acid induced the secretion of 2-3 times as much cholesterol in FO- than in CO-fed rats. Likewise, administration of bilirubin ditaurate (30 mumol/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 fish oil increases the disposition of cholesterol into bile by potentiating bile acid-dependent cholesterol secretion, presumably by facilitating the recruitment of bile-destined cholesterol.
authors.affiliation: Laboratory of Nutrition and Metabolism, University of Groningen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Smit
authors.forename: H J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: R
authors.initials: R
authors.lastname: Havinga
authors.forename: R J
authors.initials: RJ
authors.lastname: Vonk
authors.forename: G L
authors.initials: GL
authors.lastname: Scherphof
authors.forename: G
authors.initials: G
authors.lastname: In 't Veld
authors.forename: F
authors.initials: F
authors.lastname: Kuipers
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002940:Circadian Rhythm; D003314:Corn Oil / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D004041:Dietary Fats; D005395:Fish Oils; D013655:Taurochenodeoxycholic Acid; D003314:Corn Oil; D002784:Cholesterol