Regulation of the ileal bile acid-binding protein gene: an approach to determine its physiological function(s)

Ileal bile acid-binding protein (I-BABP) is a soluble bile acids (BA) carrier protein which belongs to the fatty acid-binding protein (FABP) family. In the gut, its expression is strictly restricted to the ileum, where it is thought to be involved in the active BA reabsorption. Therefore, I-BABP gene expression levels might be rate limiting for the BA enterohepatic circulation, and hence, might be crucial for cholesterol (CS) homeostasis. Indeed, BA not reclaimed by intestinal absorption constitute the main way to eliminate a CS excess. However, such a function is not yet established. Because generally rate limiting genes are tightly controlled, we have undertaken the study of the I-BABP gene regulation. It was found that both BA and CS, probably via oxysterols, are able to up-regulate the transcription rate of I-BABP gene. The fact that intracellular sterol sensors (FXR, LXR and SREBP1c) are involved in the control of I-BABP gene expression strongly suggest a crucial role for I-BABP in the ileum.