The protective effect of obeticholic acid on lipopolysaccharide-induced disorder of maternal bile acid metabolism in pregnant mice
| Autor: | Cheng Zhang, Li Ma, Wei-Rong Hu, Ming-Qiang Qin, Bing-Dong Song, Jin-Wei Lv, Weiying Jiang, Yu Gan, Jian-Qing Wang, Zhi-Bing Liu, Jian Li, Hua Wang, De-Xiang Xu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Lipopolysaccharide medicine.drug_class CYP3A Immunology Cholesterol 7 alpha-hydroxylase Chenodeoxycholic Acid Tight Junctions Bile Acids and Salts 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Pregnancy Internal medicine medicine Immunology and Allergy Animals Humans Cholesterol 7-alpha-Hydroxylase Cells Cultured Pharmacology Mice Inbred ICR Bile acid Obeticholic acid RNA-Binding Proteins Metabolism G protein-coupled bile acid receptor 030104 developmental biology Endocrinology chemistry Gene Expression Regulation Liver 030220 oncology & carcinogenesis Farnesoid X receptor Female |
| Zdroj: | International immunopharmacology. 83 |
| ISSN: | 1878-1705 |
| Popis: | The disorder of bile acid metabolism is a common feature during pregnancy, which leads to adverse birth outcomes and maternal damage effects. However, the cause and therapy about the disorder of bile acid metabolism are still poor. Microbial infection often occurs in pregnant women, which can induce the disorder of bile acid metabolism in adult mice. Here, this study observed the acute effect of lipopolysaccharide (LPS) on maternal bile acid of pregnant mice at gestational day 17 and the protective effect of obeticholic acid (OCA) pretreatment, a potent agonist of bile acid receptor farnesoid X receptor (FXR). The results showed LPS significantly increased the level of maternal serum and disordered bile acids components of maternal serum and liver, which were ameliorated by OCA pretreatment with obviously reducing the contents of CA, TCA, DCA, TCDCA, CDCA, GCA and TDCA in maternal serum and DCA, TCA, TDCA, TUDCA, CDCA and TCDCA in maternal liver. Furthermore, we investigated the effects of OCA on LPS-disrupted bile acid metabolism in maternal liver. LPS disrupted maternal bile acid profile by decreasing transport and metabolism with hepatic tight junctions of bile acid in pregnant mice. OCA obviously increased the protein level of nuclear FXR and regulated its target genes involving in the metabolism of bile acid, which was characterized by the lower expression of bile acid synthase CYP7A1, the higher expression of CYP3A and the higher mRNA level of transporter Mdr1a/b. This study provided the evidences that LPS disrupted bile acid metabolism in the late stage of pregnant mice and OCA pretreatment played the protective role on it by activating FXR. |
| Databáze: | OpenAIRE |
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