Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy

Borges Manna, L. et al. (2020) Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy. Scientific Reports, 10, 10361. (doi: 10.1038/s41598-020-67301-1) (PMID:32587408) (PMCID:PMC7316783)

Abstract

Perturbations in the intrauterine environment can result in lifelong consequences for metabolic health during postnatal life. Intrahepatic cholestasis of pregnancy (ICP) can predispose offspring to metabolic disease in adulthood, likely due to a combination of the effects of increased bile acids, maternal dyslipidemia and deranged maternal and fetal lipid homeostasis. Whereas ursodeoxycholic acid (UDCA) is a commonly used treatment for ICP, no studies have yet addressed whether it can also prevent the metabolic effects of ICP in the offspring and fetoplacental unit. We therefore analyzed the lipid profile of fetal serum from untreated ICP, UDCA-treated ICP and uncomplicated pregnancies and found that UDCA ameliorates ICP-associated fetal dyslipidemia. We then investigated the effects of UDCA in a mouse model of hypercholanemic pregnancy and showed that it induces hepatoprotective mechanisms in the fetal liver, reduces hepatic fatty acid synthase (Fas) expression and improves glucose tolerance in the adult offspring. Finally, we showed that ICP leads to epigenetic changes in pathways of relevance to the offspring phenotype. We therefore conclude that UDCA can be used as an intervention in pregnancy to reduce features of metabolic disease in the offspring of hypercholanemic mothers.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McIlvride, Dr Saraid
• Authors: Borges Manna, L., Papacleovoulou, G., Flaviani, F., Pataia, V., Qadri, A., Abu-Hayyeh, S., Mcilvride, S., Jansen, E., Dixon, P., Chambers, J., Vazquez-Lopez, M., Wahlström, A., Kitaba, N., Marschall, H.-U., Godfrey, K. M., Lillycrop, K., and Williamson, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © The Author(s) 2020
• First Published: First published in Scientific Reports 10:10361
• Publisher Policy: Reproduced under a creative commons licence