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

Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy
Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy
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.
2045-2322
Borges Manna, Luiza
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Papacleovoulou, Georgia
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Flaviani, Flavia
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Formigo-Pataia, Vanessa
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Qadri, Asaad
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Abu-Hayyeh, Shadi
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Mcilvride, Saraid
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Jansen, Eugene
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Dixon, Peter
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Chambers, Jennifer
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Vazquez Lopez, Marta
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Wahlstroem, Annika
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Kitaba, Negusse
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Marschall, Hanns-Ulrich
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Godfrey, Keith
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Lillycrop, Karen
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Williamson, Catherine
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Borges Manna, Luiza
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Papacleovoulou, Georgia
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Flaviani, Flavia
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Formigo-Pataia, Vanessa
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Qadri, Asaad
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Abu-Hayyeh, Shadi
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Mcilvride, Saraid
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Jansen, Eugene
bf70943e-b9fc-4505-8464-e1aed627202e
Dixon, Peter
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Chambers, Jennifer
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Vazquez Lopez, Marta
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Wahlstroem, Annika
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Kitaba, Negusse
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Marschall, Hanns-Ulrich
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Godfrey, Keith
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Lillycrop, Karen
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Williamson, Catherine
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Borges Manna, Luiza, Papacleovoulou, Georgia, Flaviani, Flavia, Formigo-Pataia, Vanessa, Qadri, Asaad, Abu-Hayyeh, Shadi, Mcilvride, Saraid, Jansen, Eugene, Dixon, Peter, Chambers, Jennifer, Vazquez Lopez, Marta, Wahlstroem, Annika, Kitaba, Negusse, Marschall, Hanns-Ulrich, Godfrey, Keith, Lillycrop, Karen and Williamson, Catherine (2020) Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy. Scientific Reports, 10 (1), [10361]. (doi:10.1038/s41598-020-67301-1).

Record type: Article

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.

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Accepted/In Press date: 14 May 2020
e-pub ahead of print date: 25 June 2020

Identifiers

Local EPrints ID: 442024
URI: http://eprints.soton.ac.uk/id/eprint/442024
ISSN: 2045-2322
PURE UUID: a3c77254-6309-4ee4-93ea-2ab286ffd684
ORCID for Negusse Kitaba: ORCID iD orcid.org/0000-0001-7518-9096
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489

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Date deposited: 06 Jul 2020 16:30
Last modified: 26 Nov 2021 07:17

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Contributors

Author: Luiza Borges Manna
Author: Georgia Papacleovoulou
Author: Flavia Flaviani
Author: Vanessa Formigo-Pataia
Author: Asaad Qadri
Author: Shadi Abu-Hayyeh
Author: Saraid Mcilvride
Author: Eugene Jansen
Author: Peter Dixon
Author: Jennifer Chambers
Author: Marta Vazquez Lopez
Author: Annika Wahlstroem
Author: Negusse Kitaba ORCID iD
Author: Hanns-Ulrich Marschall
Author: Keith Godfrey ORCID iD
Author: Karen Lillycrop ORCID iD
Author: Catherine Williamson

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