The Ileal Lipid Binding Protein Is Required for Efficient Absorption and Transport of Bile Acids in the Distal Portion of the Murine Small Intestine

Dana Praslickova,Lev Kolodzieyski,Enrique C Torchia,Elijah J Magrane,Brittnee L Zwicker,Luis B Agellon,Michael G Sugiyama,Antonio Moschetta

doi:10.1371/journal.pone.0050810

Dana Praslickova, Lev Kolodzieyski + Show 6 more

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https://doi.org/10.1371/journal.pone.0050810

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Abstract

The ileal lipid binding protein (ilbp) is a cytoplasmic protein that binds bile acids with high affinity. However evidence demonstrating the role of this protein in bile acid transport and homeostasis is missing. We created a mouse strain lacking ilbp (Fabp6−/− mice) and assessed the impact of ilbp deficiency on bile acid homeostasis and transport in vivo. Elimination of ilbp increased fecal bile acid excretion (54.2%, P<0.05) in female but not male Fabp6−/− mice. The activity of cholesterol 7α-hydroxylase (cyp7a1), the rate-controlling enzyme of the classical bile acid biosynthetic pathway, was significantly increased in female (63.5%, P<0.05) but not in male Fabp6−/− mice. The amount of [3H]taurocholic acid (TCA) excreted by 24 h after oral administration was 102% (P<0.025) higher for female Fabp6−/− mice whereas it was 57.3% (P<0.01) lower for male Fabp6−/− mice, compared to wild-type mice. The retained fraction of the [3H]TCA localized in the small and large intestines was increased by 22% (P<0.02) and decreased by 62.7% (P<0.01), respectively, in male Fabp6−/− mice relative wild-type mice, whereas no changes were seen in female Fabp6−/− mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (P<0.03) in both sexes of Fabp6−/− mice as compared to wild-type mice. The results demonstrate that ilbp is involved in the apical to basolateral transport of bile acids in ileal enterocytes, and is vital for the maintenance of bile acid homeostasis in the enterohepatic circulation (EHC) in mice.

Highlights

Bile acids are biological detergents produced by the liver that are needed for the absorption of dietary lipids and lipid-soluble nutrients from the lumen of the small intestine
Targeted deletion of the murine Slc10a2 gene, which encodes the ileal apical sodium-dependent bile acid transporter, and the phenotype of non-functional variants of the human SLC10A2 gene have established that asbt is the primary membrane-bound transporter involved in the active re-uptake of bile acids in the small intestine [1,2]
We provide evidence showing that ilbp is required for efficient apical to basolateral transport of conjugated bile acids in murine ileal enterocytes

Summary

Introduction

Bile acids are biological detergents produced by the liver that are needed for the absorption of dietary lipids and lipid-soluble nutrients from the lumen of the small intestine. These amphipathic molecules are efficiently recovered by ileal enterocytes and returned to the liver via the portal vein. Targeted deletion of the murine Slc10a2 gene, which encodes the ileal apical sodium-dependent bile acid transporter (asbt), and the phenotype of non-functional variants of the human SLC10A2 gene have established that asbt is the primary membrane-bound transporter involved in the active re-uptake of bile acids in the small intestine [1,2]. In contrast to the cellular import and export of bile acids, the mechanism for the transport of bile acids from the apical to basolateral membranes in ileal enterocytes is not clear

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