Fig. 7.

Proposed scheme for a possible role of FGF15 in the regulation of SI P450 expression. In WT mice, FGF15 not only suppresses hepatic CYP7A1 expression but also somehow hinders the activation of intestinal CYP3A expression by PXR (and/or other related nuclear receptors), which is activated by both endogenous ligands such as BAs and exogenous ligands. In the LCN mice, the loss of hepatic POR/P450 function leads to blockage of the rate-limiting enzyme (CYP7A1) in BA synthesis and severe decreases in BA levels. The latter event causes large reductions in intestinal expression of FGF15, leading to upregulation of hepatic CYP7A1 expression, as well as stimulation of intestinal CYP3A expression. +, activation of receptor; “+” with circle, activation of transcription; “−” with circle, suppression of expression.