Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly
identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type
mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic
cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR
null mice also had reduced bile acid pools and reduced fecal bile acid excretion due
to decreased expression of the major hepatic canalicular bile acid transport protein.
Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal
bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing
the regulatory role of FXR/BAR for the expression of these genes in vivo. These data
demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue
of its role as an intracellular bile acid sensor.