ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation

Abstract

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.

Asociación de los niveles de ácidos biliares y hormonas tiroideas en la colestasis intrahepática del embarazo

“…Una vía enzimática de múltiples pasos logra esto, y la síntesis está mediada en parte por el primer paso limitante de la tasa, la hidroxilación 7-alfa del colesterol, la enzima CYP7A1 del citocromo P450 (24) . Las hormonas progesterona y estrógeno, cuyas concentraciones aumentan a medida que avanza el embarazo, contribuyen a las modificaciones en el metabolismo de los ácidos biliares (25) . El estrógeno y sus metabolitos aumentan la actividad de la enzima CYP7A1 y provocan un aumento del nivel de ácidos biliares.…”

“…El estrógeno y sus metabolitos aumentan la actividad de la enzima CYP7A1 y provocan un aumento del nivel de ácidos biliares. La progesterona tiene un efecto similar a través de los receptores, y debido al aumento de los niveles de estas hormonas durante el embarazo, se produce un aumento del nivel de ABT, aunque ligero, en el embarazo normal (25) .…”

Bile Acids in Intrahepatic Cholestasis of Pregnancy

“…As a result, most of the synthesized BAs pass into the fetal blood serum, then a small fraction is excreted via the fetal kidneys into the amniotic fluid, and the remainder, the greater part, is eliminated through the placenta into the mother’s body. Most of the fetal pool of BAs is eliminated from the mother’s body via the gastrointestinal tract [ 84 , 85 ]. The identified factors influencing the maintenance of BA balance in the maternal-fetal circulation include: activity of hepatic metabolic pathways involved in the biosynthesis and transformation of BAs in both the mother and the fetus, the rate of BA elimination from the maternal organism, and the transport properties of the placenta [ 81 , 86 ].…”

Manejo da colestase intra-hepática gestacional / Gestational intrahepatic cholestase management

“…Quanto a sintomatologia da doença, seu início é insidioso, por volta do segundo trimestre de gestação (pode surgir também no terceiro semestre) com quadro clínico de prurido crescente, em alguns casos, pode haver leves queixas álgicas em hipocôndrio direito acompanhadas de náuseas, anorexia, insônia e esteatorreia. Ao exame físico, geralmente, é encontrado escoriações por conta do prurido (8) .…”