Nikolova Vanya, Mitchell Alice L, Bellafante Elena, Jansen Eugene, Papacleovoulou Georgia, Bergh Per-Olof, Marshall Hanns-Ulrich, Williamson Catherine
Department of Women and Children's Health, Guy's Campus, King's College London, London, UK.
Department of Metabolism, Digestion and Reproduction, Hammersmith Campus, Imperial College London, London, UK.
Physiol Rep. 2024 Dec;12(23):e70141. doi: 10.14814/phy2.70141.
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.
患有妊娠期肝内胆汁淤积症（ICP）的女性存在高胆血症，同时血脂异常风险增加。我们研究了在小鼠孕期补充胆酸（CA）如何影响脂肪组织功能。从小鼠交配栓识别开始至妊娠第14天或15天，给小鼠喂食正常饲料或添加0.5% CA的饲料（每组n = 10 - 11只），并与未怀孕小鼠进行实验匹配（每组n = 7只）。测量组织重量以及血浆胆汁酸、葡萄糖、脂质、活性氧代谢产物（ROM）和脂肪因子。评估皮下和性腺脂肪细胞的mRNA表达。补充CA可抑制与妊娠相关的脂肪组织扩张并降低胎儿体重。孕期CA饮食会增加低密度脂蛋白胆固醇并降低高密度脂蛋白胆固醇。妊娠和CA饮食会降低脂肪细胞中脂质代谢转录物的表达。孕期补充CA可使血浆ROM增加1.24倍，并分别使炎症调节蛋白pentraxin - 2/3和胰岛素样生长因子1（IGF - 1）水平降低>50%和>80%。我们共同表明，高胆血症会扰乱妊娠后期与妊娠相关的脂肪组织扩张和mRNA表达，同时伴有IGF - 1降低、脂质可用性改变以及炎症和氧化增加，这可能会影响胎儿生长。这项工作强调了更好地了解ICP妊娠中脂肪组织和氧化还原应激变化及其对胎儿健康潜在影响的必要性。
