Gestational hypercholanemia suppresses pregnancy-associated adipose mass increase and stimulates a pro-inflammatory environment in mice
Author(s)
Type
Journal Article
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.
Date Issued
2024-12-01
Date Acceptance
2024-11-21
Citation
Physiological Reports, 2024, 12 (23)
ISSN
2051-817X
Publisher
Wiley
Journal / Book Title
Physiological Reports
Volume
12
Issue
23
Copyright Statement
© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39667808
Subjects
ABSORPTION
adipocyte
CHOLIC-ACID
fetal growth restriction
GROWTH
hypercholanemia
hyperlipidemia
INTRAHEPATIC CHOLESTASIS
intrahepatic cholestasis of pregnancy
Life Sciences & Biomedicine
MATERNAL CHOLESTASIS
METABOLISM
Physiology
Science & Technology
Publication Status
Published
Coverage Spatial
United States
Article Number
e70141
Date Publish Online
2024-12-12