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Cited by 592

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine

Open access
Kim, Insook, Ahn, Sung-Hoon, Inagaki, Takeshi, Choi, Mihwa, Ito, Shinji, Guo, Grace L., Kliewer, Steven A., Gonzalez, Frank J.·2007·Journal of Lipid Research

Abstract

Bile acid concentrations are controlled by a feedback regulatory pathway whereby activation of the farnesoid X receptor (FXR) represses transcription of both the CYP7A1 gene, encoding the rate-limiting enzyme in the classic bile acid synthesis pathway, and the CYP8B1 gene, required for synthesis of cholic acid. The tissue-specific roles of FXR were examined using liver- and intestine-specific FXR-null models. FXR deficiency in either liver (Fxr DeltaL) or intestine (Fxr DeltaIE) increased bile acid pool size. Treatment with the FXR-selective agonist GW4064 significantly repressed CYP7A1 in Fxr DeltaL mice but not Fxr DeltaIE mice, demonstrating that activation of FXR in intestine but not liver is required for short-term repression of CYP7A1 in liver. This intestinal-specific effect of FXR is likely mediated through induction of the hormone FGF15, which suppresses CYP7A1. In comparison to CYP7A1, FXR-mediated repression of CYP8B1 was more dependent on the presence of FXR in liver and less dependent on its presence in intestine. Consistent with these findings, recombinant FGF15 repressed CYP7A1 mRNA levels without affecting CYP8B1 expression. These data provide evidence that FXR-mediated repression of bile acid synthesis requires the complementary actions of FXR in both liver and intestine and reveal mechanistic differences in feedback repression of CYP7A1 and CYP8B1.

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Metadata

Authors
Kim, I., Ahn, S.-H., Inagaki, T., Choi, M., Ito, S., Guo, G. L., Kliewer, S. A., & Gonzalez, F. J.
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2007-12
Volume
48
Issue
12
Pages
2664-2672
ISSN
0022-2275 (ISSN-L)
OpenAlex
W2152035679
Cited by
592
References
40
FWCI
9.96
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. https://app.cochat.ai/papers/10.1194/jlr.m700330-jlr200
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Kim, I., Ahn, S.-H., Inagaki, T., Choi, M., Ito, S., Guo, G. L., Kliewer, S. A., & Gonzalez, F. J. (2007). Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. Journal of Lipid Research. https://doi.org/10.1194/jlr.m700330-jlr200

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