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Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition

J Lipid Res. 2020; 
Honda A, Miyazaki T, Iwamoto J, Hirayama T, Morishita Y, Monma T, Ueda H, Mizuno S, Sugiyama F, Takahashi S, Ikegami T.
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摘要

The bile acid (BA) composition in mice is substantially different from that in humans. Chenodeoxycholic acid (CDCA) is an end product in the human liver; however, mouse Cyp2c70 metabolizes CDCA to hydrophilic muricholic acids (MCAs). Moreover, in humans, the gut microbiota converts the primary BAs, cholic acid and CDCA, into deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. In contrast, the mouse Cyp2a12 reverts this action and converts these secondary BAs to primary BAs. Here, we generated Cyp2a12 KO, Cyp2c70 KO, and Cyp2a12/Cyp2c70 double KO (DKO) mice using the CRISPR-Cas9 system to study the regulation of BA metabolism under hydrophobic BA composition. Cyp2a12 KO mice showed the accumulation ... More

关键词

7α-hydroxy-4-cholesten-3-one 12α-hydroxylase; CRISPR-Cas9; CYP2A12; CYP2C70; cholesterol 7α-hydroxylase; cytochrome P450; cytokines; farnesoid X receptor; knockout mouse; pregnane X receptor