On the Evolution of Bile Salts and the Farnesoid X Receptor in Vertebrates

Abstract

In recent decades, our knowledge of bile salts has undergone a vast development, and bile salts are now known not only for their detergent properties that aid in the absorption of dietary lipids but also for their interaction with specific nuclear and membrane receptors. In particular, it has been realized that the response of the farnesoid X receptor (FXR) to bile acids provides a signal bridge between the liver and small intestine, controlling the intracellular levels, biosynthesis, and enterohepatic circulation of bile acids. Therefore, FXR and bile acid signaling has become an attractive target for treatment of, for example, cholestatic liver diseases, diabetes, and colorectal cancer. Previously, interest in the structure and chemistry of bile salts has focused on their cellular toxicity and involvement in digestion. However, insight into the extensive variation in the structure of bile salts in vertebrates and the concurrent evolution of the FXR has become increasingly important as their role as signal molecules has become clearer. In this review, we therefore focus on common structural features of bile salts as well as evolutionary aspects of bile salts and the FXR in vertebrates. Ultimately, a better understanding of the evolution of bile salts and the FXR may expand our knowledge of their function in health and disease, including their function outside the gastrointestinal tract, and aid in the development of new strategies for treatment.

Keywords: FXR; bile acids; bile alcohols; biosynthesis; cholesterol; enterohepatic circulation; metabolism; nuclear receptors.