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

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

<div><p>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 (<em>Fabp6^−/−</em> 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%, <em>P</em><0.05) in female but not male <em>Fabp6^−/−</em> 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%, <em>P</em><0.05) but not in male <em>Fabp6^−/−</em> mice. The amount of [³H]taurocholic acid (TCA) excreted by 24 h after oral administration was 102% (<em>P</em><0.025) higher for female <em>Fabp6^−/−</em> mice whereas it was 57.3% (<em>P</em><0.01) lower for male <em>Fabp6^−/−</em> mice, compared to wild-type mice. The retained fraction of the [³H]TCA localized in the small and large intestines was increased by 22% (<em>P</em><0.02) and decreased by 62.7% (<em>P</em><0.01), respectively, in male <em>Fabp6^−/−</em> mice relative wild-type mice, whereas no changes were seen in female <em>Fabp6^−/−</em> mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (<em>P</em><0.03) in both sexes of <em>Fabp6^−/−</em> 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.</p> </div

Survey of gene expression in the small intestine.

<p>(A) qPCR analysis of RNA from small intestines of <i>Fabp6</i>^+/+ (black bars) and <i>Fabp6^−/−</i> (white bars) were done in duplicates. The normalized abundance (mean±SEM) of target mRNAs is expressed relative to male <i>Fabp6</i>^+/+ mice. <i>P</i><0.05, vs. wild-type of the same sex. (B) Protein blots of small intestine homogenates of <i>Fabp6</i>^+/+ and <i>Fabp6^−/−</i> mice were probed with antisera to ilbp, asbt and L-FABP.</p

Plasma chemistry.

*<p>P<0.01,</p>**<p>P<0.05, vs. wild-type, n = 10 per group. Values for ALT and AST are mean ± SEM.</p