Zhang Boyan, Kuipers Folkert, de Boer Jan Freark, Kuivenhoven Jan Albert
Department of Pediatrics, University Medical Centre Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
J Clin Med. 2021 Dec 21;11(1):4. doi: 10.3390/jcm11010004.
New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Changes in bile acid metabolism, however, translate into an alteration of plasma cholesterol and triglyceride concentrations, which may also affect cardiovascular outcomes in such patients. This review attempts to gain insight into this matter and improve our understanding of the interactions between bile acid and lipid metabolism. Bile acid sequestrants (BAS), which bind bile acids in the intestine and promote their faecal excretion, have long been used in the clinic to reduce LDL cholesterol and, thereby, atherosclerotic cardiovascular disease (ASCVD) risk. However, BAS modestly but consistently increase plasma triglycerides, which is considered a causal risk factor for ASCVD. Like BAS, inhibitors of the apical sodium-dependent bile acid transporter (ASBTi's) reduce intestinal bile acid absorption. ASBTi's show effects that are quite similar to those obtained with BAS, which is anticipated when considering that accelerated faecal loss of bile acids is compensated by an increased hepatic synthesis of bile acids from cholesterol. Oppositely, treatment with farnesoid X receptor agonists, resulting in inhibition of bile acid synthesis, appears to be associated with increased LDL cholesterol. In conclusion, the increasing efforts to employ drugs that intervene in bile acid metabolism and signalling pathways for the treatment of metabolic diseases such as NAFLD warrants reinforcing interactions between the bile acid and lipid and lipoprotein research fields. This review may be considered as the first step in this process.
目前，针对胆汁酸代谢的新型药物正在进行临床研究，以评估其治疗胆汁淤积性肝病、非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的潜力。然而，胆汁酸代谢的变化会导致血浆胆固醇和甘油三酯浓度的改变，这也可能影响此类患者的心血管结局。本综述旨在深入探讨这一问题，增进我们对胆汁酸与脂质代谢之间相互作用的理解。胆汁酸螯合剂（BAS）可在肠道内结合胆汁酸并促进其粪便排泄，长期以来一直用于临床降低低密度脂蛋白胆固醇，从而降低动脉粥样硬化性心血管疾病（ASCVD）风险。然而，BAS会适度但持续地升高血浆甘油三酯，而这被认为是ASCVD的一个因果风险因素。与BAS类似，顶端钠依赖性胆汁酸转运体抑制剂（ASBTi）可减少肠道胆汁酸吸收。ASBTi的作用与BAS相当相似，考虑到胆汁酸粪便排泄加速会通过肝脏从胆固醇合成胆汁酸的增加来代偿，这是可以预期的。相反，法尼酯X受体激动剂治疗会抑制胆汁酸合成，似乎与低密度脂蛋白胆固醇升高有关。总之，越来越多地努力使用干预胆汁酸代谢和信号通路的药物来治疗NAFLD等代谢性疾病，这就需要加强胆汁酸与脂质及脂蛋白研究领域之间的相互作用。本综述可被视为这一过程的第一步。
