title: Bile Acid Uptake Transporters as Targets for Therapy.
abstract: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Davor
authors.initials: D
authors.lastname: Slijepcevic
authors.forename: Stan F J
authors.initials: SF
authors.lastname: van de Graaf
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002779:Cholestasis / Q000378:metabolism; D004764:Enterohepatic Circulation; D006801:Humans; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D058990:Molecular Targeted Therapy
chemical_list: D001647:Bile Acids and Salts; D026901:Membrane Transport Proteins