Spinelli Valeria, Chávez-Talavera Oscar, Tailleux Anne, Staels Bart
aUniv Lille, UMR1011, EGID bInserm, UMR1011 cCHU Lille dInstitut Pasteur de Lille, U1011, Lille, France *Valeria Spinelli and Oscar Chávez-Talavera have contributed equally to the writing of this article.
Curr Opin Endocrinol Diabetes Obes. 2016 Apr;23(2):138-44. doi: 10.1097/MED.0000000000000235.
This article discusses the impact of bile acid sequestrants (BAS) on cardiovascular risk factors (CVRFs), on the basis of recent (pre)clinical studies assessing the metabolic impact of modulation of enterohepatic bile acid signaling via the bile acid receptors farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5).
BAS decrease low-density lipoprotein-cholesterol by stimulating de novo hepatic bile acid synthesis and lowering intestinal lipid absorption, and improve glucose homeostasis in type 2 diabetes mellitus, at least in part by increasing GLP-1 production, via intestinal TGR5- and FXR-dependent mechanisms. Intestinal and peripheral FXR and TGR5 modulation also affects peripheral tissues, which can contribute to the reduction of CVRFs.
Bile acids are regulators of metabolism acting in an integrated interorgan manner via FXR and TGR5. Modulation of the bile acid pool size and composition, and selective interference with their receptors could, therefore, be a therapeutic approach to decrease CVRFs. Even though clinical cardiovascular outcome studies using BAS are still lacking, the existing data point to BAS as an efficacious pharmacological approach to reduce CVRFs.
本文基于近期评估通过胆汁酸受体法尼酯X受体（FXR）和武田G蛋白偶联受体5（TGR5）调节肝肠胆汁酸信号传导的代谢影响的（临床前）研究，探讨胆汁酸螯合剂（BAS）对心血管危险因素（CVRF）的影响。
BAS通过刺激肝脏从头合成胆汁酸和降低肠道脂质吸收来降低低密度脂蛋白胆固醇，并改善2型糖尿病患者的血糖稳态，至少部分是通过肠道TGR5和FXR依赖机制增加胰高血糖素样肽-1（GLP-1）的产生来实现的。肠道和外周FXR及TGR5的调节也会影响外周组织，这有助于降低CVRF。
胆汁酸是通过FXR和TGR5以器官间整合方式发挥作用的代谢调节因子。因此，调节胆汁酸池大小和组成以及对其受体的选择性干扰可能是降低CVRF的一种治疗方法。尽管仍缺乏使用BAS的临床心血管结局研究，但现有数据表明BAS是降低CVRF的一种有效药理学方法。
