Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
Eur J Endocrinol. 2021 Mar;184(3):R69-R83. doi: 10.1530/EJE-20-1101.
Bile acids are lipid-solubilising molecules that also regulate metabolic processes. Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) are two bile acid receptors with key metabolic roles. FXR regulates bile acid synthesis in the liver and influences bile acid uptake in the intestine. TGR5 is mainly involved in regulation of signalling pathways in response to bile acid uptake in the gut and therefore prandial response. Both FXR and TGR5 have potential as therapeutic targets for disorders of glucose and/or lipid homeostasis. Gestation is also known to cause small increases in bile acid concentrations, but physiological hypercholanaemia of pregnancy is usually not sufficient to cause any clinically relevant effects. This review focuses on how gestation alters bile acid homeostasis, which can become pathological if the elevation of maternal serum bile acids is more marked than physiological hypercholanaemia, and on the influence of FXR and TGR5 function in pregnancy on glucose and lipid metabolism. This will be discussed with reference to two gestational disorders: intrahepatic cholestasis of pregnancy (ICP), a disease where bile acids are pathologically elevated, and gestational diabetes mellitus (GDM), characterised by hyperglycaemia during pregnancy.
胆汁酸是具有脂溶性的分子，也能调节代谢过程。法尼醇 X 受体（FXR）和 Takeda G 蛋白偶联受体 5（TGR5）是两种具有关键代谢作用的胆汁酸受体。FXR 调节肝脏中的胆汁酸合成，并影响肠道中的胆汁酸摄取。TGR5 主要参与肠道中胆汁酸摄取后的信号通路的调节，因此影响进食反应。FXR 和 TGR5 都有可能成为葡萄糖和/或脂质稳态紊乱的治疗靶点。妊娠也已知会导致胆汁酸浓度略有升高，但生理性妊娠高胆固醇血症通常不足以引起任何临床相关的影响。本综述重点介绍妊娠如何改变胆汁酸稳态，如果母体血清胆汁酸升高超过生理性高胆固醇血症，则会导致病理变化，以及妊娠中 FXR 和 TGR5 功能对葡萄糖和脂质代谢的影响。这将参考两种妊娠疾病进行讨论：妊娠肝内胆汁淤积症（ICP），胆汁酸病理性升高的疾病，以及妊娠糖尿病（GDM），其特征是妊娠期间血糖升高。
