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  • 标题:Dietary fish oil potentiates bile acid-induced cholesterol secretion into bile in rats.
  • 本地全文:下载
  • 作者:M J Smit ; H J Verkade ; R Havinga
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:1994
  • 卷号:35
  • 期号:2
  • 页码:301-310
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要: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.
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