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

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.

Direct Comparison of Mice Null for Liver or Intestinal Fatty Acid-binding Proteins Reveals Highly Divergent Phenotypic Responses to High Fat Feeding

“…Thus, LFABP is involved in trafficking of dietderived MG under all dietary conditions examined, consistent with it being the MG binding and transport protein in cytosol (9). Analysis of ILBP ablated mice demonstrated a defect in mucosal to serosal transport of taurocholic acid in everted gut sacs and supports the idea that FABPs are involved in the cellular transport of their respective ligands (72).…”

Identification, visualization and clonal analysis of intestinal stem cells in fish

“…Like apoa1 , medaka fabp2 was expressed only in the first four gut segments (S1-S4). In mammals, Fabp6 acts as an intracellular transporter of bile acids in ileal epithelial cells (most distal part of the small intestine), helping to catalyse and to metabolize cholesterol (Praslickova et al, 2012). In medaka, fabp6 expression was detected in segments S3-S6, with a very weak expression in S1 and S2 (Fig.…”

Intestinal transport and metabolism of bile acids

“…However, because FXR regulates many different genes and pathways ( 1 ), it was diffi cult to draw specifi c conclusions regarding the in vivo role of IB-ABP from those models. New insights to that question come from a recent study using an IBABP-null mouse model ( 84 ). In that study, mucosal-to-serosal transport of taurocholate was signifi cantly reduced in ileal gut sacs prepared from male and female IBABP-null mice.…”