Slijepcevic Davor, van de Graaf Stan F J
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
Dig Dis. 2017;35(3):251-258. doi: 10.1159/000450983. Epub 2017 Mar 1.
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.
胆汁酸是强大的信号分子，主要通过胆汁酸受体法尼醇X受体（FXR）和跨膜G蛋白偶联受体5（TGR5）来调节葡萄糖、脂质和能量稳态。牛磺胆酸钠共转运多肽（NTCP）和顶端钠依赖性胆汁酸转运体（ASBT）确保（结合型）胆汁酸的有效循环。这些转运蛋白的调节会影响胆汁酸的定位、动态变化和信号传导。NTCP特异性药理抑制剂myrcludex B可抑制肝脏对结合型胆汁酸的摄取。多种ASBT抑制剂已进入临床试验阶段，用于抑制肠道胆汁酸的摄取。在此，我们讨论了目前关于靶向胆汁酸摄取转运体对全身和肠道胆汁酸动态变化影响的见解，并探讨了由此产生的可能治疗应用。
