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. 2019 Dec 20;9:19493. doi: 10.1038/s41598-019-55988-w

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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OCA treatment reduces hepatic retinyl palmitate, while increasing retinol levels in mouse livers. Control and OCA-treated mice were analyzed for hepatic vitamin A levels, mRNA and protein levels of FXR targets and vitamin A metabolizing factors. (A) The mRNA levels of FXR target genes Nr0b2 (encoding SHP) and Abcb11 (encoding BSEP) were strongly enhanced in livers of OCA-treated mice. (B) Hepatic retinyl palmitate levels were significantly reduced in OCA-treated mice, while hepatic retinol levels were significantly increased as compared to control mice. (C) Hepatic mRNA levels of Lrat, Rbp4 and Pnpla3 were not changed, while levels of Pnpla2 (ATGL) were decreased and Lipe (HSL) were increased in OCA-treated mice. (D) Protein levels of LRAT were not affected by OCA-treatment, while RBP4, ATGL, PNPLA3, HSL (and its active phosphorylated form pHSL), CYP7A1 and NTCP were all decreased and PEPCK was increased. GAPDH was used as loading control. (E) mRNA levels of genes involved in the conversion of retinol into retinoic acid (Raldh1, Raldh2, Raldh4) and of (F) retinoic acid-responsive genes (Cpt1a, Pck1, Ppargc1a, Cyp26a1, Ucp2, Fgf21) were enhanced in OCA-treated mice as compared to control animals. Data are presented as Mean ± SEM and mRNA expression of genes is presented in 2^{−delta CT}, which was normalized to 36B4.