Question

In the intestine, bile acids binding to the FXR increase expression of target genes while in the liver target gene expression is decreased. Describe the basis for these effects.

Answer 1

Regulation of bile acid synthesis and effect in small intestine and liver after binding with FXR is established a crosstalk mechanism. FXR is a tissue specific nuclear receptor found in both liver and small intestine showing differnt effect. FRX in liver decrases new synthesis of bile acids while incrases bile acids secretion in small intestine.

Inside liver, FRX activation promotes the expression of SHP molecule (small heterodimer partner), which then interact with liver receptors (LRH-1) , thereby decreasing its activity. There are some ABC transporters are also present which coninuously export bile acids by bile salt export pump (ABCA11) and multidrug protein (MRP2 or ABCC2). Resulting to this it inhibits the expression of targated genes. Regulation of above these trasporter are very important in order to prevent bile acids accumulation in liver.and therby hepatic injury.

While in intestine the scenario is reverse, in small intestine bile acids are actively absorbed by the ASBT (apical sodium dependent bile acid transporter ) Bile acids dependent FXR activation in the ileum promotes the FGF19/15, which furhter form complexes with other growth factor resulting in active expression of targated genes.