Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice
Abstract Women with intrahepatic cholestasis of pregnancy (ICP) have hypercholanemia alongside an increased risk of dyslipidemia. We investigated how cholic acid (CA) supplementation in murine pregnancy impacts adipose tissue function. Mice were fed normal or 0.5% CA‐supplemented chow from identific...
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2024-12-01
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| Online Access: | https://doi.org/10.14814/phy2.70141 |
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| author | Vanya Nikolova Alice L. Mitchell Elena Bellafante Eugene Jansen Georgia Papacleovoulou Per‐Olof Bergh Hanns‐Ulrich Marshall Catherine Williamson |
| author_facet | Vanya Nikolova Alice L. Mitchell Elena Bellafante Eugene Jansen Georgia Papacleovoulou Per‐Olof Bergh Hanns‐Ulrich Marshall Catherine Williamson |
| author_sort | Vanya Nikolova |
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| description | Abstract Women with intrahepatic cholestasis of pregnancy (ICP) have hypercholanemia alongside an increased risk of dyslipidemia. We investigated how cholic acid (CA) supplementation in murine pregnancy impacts adipose tissue function. Mice were fed normal or 0.5% CA‐supplemented chow from identification of copulatory plug until gestational day 14 or 15 (n = 10–11/group) and were matched experimentally with nonpregnant mice (n = 7/group). Tissue weights were measured alongside plasma bile acids, glucose, lipids, reactive oxygen metabolites (ROM), and adipokines. Subcutaneous and gonadal adipocyte mRNA expression was evaluated. CA supplementation inhibited pregnancy‐associated adipose tissue expansion and decreased fetal weight. CA diet in pregnancy increased LDL‐cholesterol and reduced HDL‐cholesterol. Pregnancy and CA diet reduced lipid metabolism transcript expression in adipocytes. CA supplementation during pregnancy increased plasma ROM by 1.24‐fold and suppressed inflammatory‐modulating pentraxin‐2/3 and insulin‐like growth factor 1 (IGF‐1) levels by >50% and >80%, respectively. Together, we show that hypercholanemia disturbs pregnancy‐associated adipose tissue expansion and mRNA expression in late gestation concomitant with reduced IGF‐1, altered lipid availability and increased inflammation and oxidation, which could impact fetal growth. This work highlights the need to better understand adipose tissue and redox stress changes in ICP pregnancies and the potential implications for fetal health. |
| format | Article |
| id | doaj-art-2817727590a14ff1861a9b72fd8b37dc |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| spelling | doaj-art-2817727590a14ff1861a9b72fd8b37dc2025-01-10T11:14:29ZengWileyPhysiological Reports2051-817X2024-12-011223n/an/a10.14814/phy2.70141Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in miceVanya Nikolova0Alice L. Mitchell1Elena Bellafante2Eugene Jansen3Georgia Papacleovoulou4Per‐Olof Bergh5Hanns‐Ulrich Marshall6Catherine Williamson7Department of Women and Children's Health, Guy's Campus King's College London London UKDepartment of Women and Children's Health, Guy's Campus King's College London London UKDepartment of Women and Children's Health, Guy's Campus King's College London London UKCentre for Health Protection, National Institute for Public Health and the Environment Bilthoven The NetherlandsDepartment of Women and Children's Health, Guy's Campus King's College London London UKThe Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenThe Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenDepartment of Women and Children's Health, Guy's Campus King's College London London UKAbstract Women with intrahepatic cholestasis of pregnancy (ICP) have hypercholanemia alongside an increased risk of dyslipidemia. We investigated how cholic acid (CA) supplementation in murine pregnancy impacts adipose tissue function. Mice were fed normal or 0.5% CA‐supplemented chow from identification of copulatory plug until gestational day 14 or 15 (n = 10–11/group) and were matched experimentally with nonpregnant mice (n = 7/group). Tissue weights were measured alongside plasma bile acids, glucose, lipids, reactive oxygen metabolites (ROM), and adipokines. Subcutaneous and gonadal adipocyte mRNA expression was evaluated. CA supplementation inhibited pregnancy‐associated adipose tissue expansion and decreased fetal weight. CA diet in pregnancy increased LDL‐cholesterol and reduced HDL‐cholesterol. Pregnancy and CA diet reduced lipid metabolism transcript expression in adipocytes. CA supplementation during pregnancy increased plasma ROM by 1.24‐fold and suppressed inflammatory‐modulating pentraxin‐2/3 and insulin‐like growth factor 1 (IGF‐1) levels by >50% and >80%, respectively. Together, we show that hypercholanemia disturbs pregnancy‐associated adipose tissue expansion and mRNA expression in late gestation concomitant with reduced IGF‐1, altered lipid availability and increased inflammation and oxidation, which could impact fetal growth. This work highlights the need to better understand adipose tissue and redox stress changes in ICP pregnancies and the potential implications for fetal health.https://doi.org/10.14814/phy2.70141adipocytefetal growth restrictionhypercholanemiahyperlipidemiaintrahepatic cholestasis of pregnancy |
| spellingShingle | Vanya Nikolova Alice L. Mitchell Elena Bellafante Eugene Jansen Georgia Papacleovoulou Per‐Olof Bergh Hanns‐Ulrich Marshall Catherine Williamson Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice Physiological Reports adipocyte fetal growth restriction hypercholanemia hyperlipidemia intrahepatic cholestasis of pregnancy |
| title | Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice |
| title_full | Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice |
| title_fullStr | Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice |
| title_full_unstemmed | Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice |
| title_short | Gestational hypercholanemia suppresses pregnancy‐associated adipose mass increase and stimulates a pro‐inflammatory environment in mice |
| title_sort | gestational hypercholanemia suppresses pregnancy associated adipose mass increase and stimulates a pro inflammatory environment in mice |
| topic | adipocyte fetal growth restriction hypercholanemia hyperlipidemia intrahepatic cholestasis of pregnancy |
| url | https://doi.org/10.14814/phy2.70141 |
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