Metabolic impact of bile acids in gestation

Bile acids are lipid-solubilising molecules that also regulate metabolic processes. Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGRS) 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 TGRS 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.

Automated summary

This article discusses the metabolic regulation of bile acids and their impact on bile acid homeostasis and metabolism during pregnancy, focusing on the roles of FXR and TGR5 in glucose and lipid metabolism during pregnancy, as well as their potential applications in gestational disorders such as ICP and GDM.