Mechanism of Biliary Lipid Secretion in the Rat: A Role for Bile Acid-independent Bile Flow?

HJ Verkade*, H Wolters, A Gerding, R Havinga, Vaclav Fidler, RJ Vonk, F Kuipers

*Corresponding author for this work

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    Abstract

    Bile acid-induced lipid secretion was compared in unanesthetized normal control and Groningen Yellow Wistar rats during variations in endogenous bile acid output. Groningen Yellow rats express a genetic defect in the biliary secretion of various organic anions. During a 5-hr period after interruption of the enterohepatic circulation, bile acid secretion decreased from 36.4 +/- 1.8 to 1.9 +/- 0.3 mumol per 30 min in normal control rats and from 37.1 +/- 2.8 to 1.8 +/- 0.2 mumol per 30 min in Groningen Yellow rats, respectively (mean +/- S.E.M., n = 5). The relationship between bile acid secretion and bile flow showed similar slopes (normal control, 8.74 +/- 0.44 mul/mumol and Groningen Yellow rats, 7.71 +/- 0.42 mul/mumol) but different y-intercepts (normal control, 243 +/- 8 and Groningen Yellow, 127 +/- 4 mul per 30 min; p <0.001), corresponding to a 47% reduction of the bile acid-independent fraction of bile flow in Groningen Yellow rats. During the course of the experiment, the ratio of lipids (phospholipids plus cholesterol) to bile acids increased in both strains more than threefold but was permanently higher in Groningen Yellow than in normal control rats (p = 0.035), implying that Groningen Yellow rats continuously secreted more lipid per bile acid. No differences in bile acid pool composition or in bile canalicular membrane composition and fluidity between the two strains were detected. The results indicate that apart from previously demonstrated factors (bile acid concentration, bile acid composition and hydrophilic organic anion concentration in bile), another parameter affects the efficacy of bile acids to induce biliary lipid secretion. We hypothesize that the magnitude of bile acid-independent flow is a coregulating factor by influencing the exposure time of the canalicular membrane to intracanalicular bile acids.

    Original languageEnglish
    Pages (from-to)1074-1080
    Number of pages7
    JournalHepatology
    Volume17
    Issue number6
    Publication statusPublished - Jun-1993

    Keywords

    • ORGANIC-ANIONS
    • GUINEA-PIG
    • CHOLESTEROL
    • EXCRETION
    • TRANSPORT
    • CHROMATOGRAPHY
    • BILIRUBIN
    • HAMSTER

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