Bile salts in control of lipid metabolism

The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of interactions between bile salts and lipid metabolism, with a particular emphasis on the underlying mechanisms. The nuclear receptor farnesoid X receptor (FXR) plays major roles in bile salt-mediated signaling pathways. The recent identification of novel FXR targets and factors involved in FXR signaling highlights the interactions of bile acids with lipid metabolism. Exciting data have been reported on the use of intestine-specific FXR agonists as well as antagonists. In addition, encouraging results for treatment of hepatic steatosis obtained with obeticholic acid in the FLINT trial underline the therapeutic potential of bile salt signaling and metabolism for the treatment of lipid disorders. Modulation of FXR activity appears to be a potent target, not only for improving bile salt homeostasis, but also to improve lipid metabolism. Depending on the metabolic context both, FXR agonists as well as antagonists, could prove to be of therapeutic benefit