Cited by 196Drug Transport and Resistance MechanismsFibroblast Growth Factor ResearchCholesterol and Lipid Metabolism

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Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

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Katafuchi, Takeshi, Makishima, Makoto·2022·International Journal of Molecular Sciences

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Abstract

Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones. Farnesoid X receptor (FXR) is a nuclear receptor that forms a heterodimer with retinoid X receptor α (RXRα), is activated by BAs in the enterohepatic circulation reabsorbed via transporters in the ileum and the colon, and plays a critical role in regulating gene expression involved in cholesterol, BA, and lipid metabolism in the liver. The FXR/RXRα heterodimer also exists in the distal ileum and regulates production of fibroblast growth factor (FGF) 15/FGF19, a hormone traveling via the enterohepatic circulation that activates hepatic FGF receptor 4 (FGFR4)-β-klotho receptor complex and regulates gene expression involved in cholesterol, BA, and lipid metabolism, as well as those regulating cell proliferation. Agonists for FXR and analogs for FGF15/19 are currently recognized as a promising therapeutic target for metabolic syndrome and cholestatic diseases.

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Authors: Katafuchi, T., & Makishima, M.
Affiliations: Nihon University (JP)
Corresponding author: Katafuchi, Takeshi
ORCID: Katafuchi, Takeshi
Makishima, Makoto
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2022-05-27
Volume: 23
Issue: 11
Pages: 6046
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms23116046
PMC: PMC9181207
OpenAlex: W4281710331
Cited by: 193
References: 183
Citations by year: 2026: 69 · 2025: 52 · 2024: 38 · 2023: 25 · 2022: 9
FWCI: 3.81
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science KAKENHI (20K22746)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords: bile acids, farnesoid X receptor, FGF receptor 4, β-Klotho, enterohepatic circulation, nuclear receptor signaling, retinoid X receptor alpha, bile acid metabolism, lipid metabolism, cholesterol metabolism, metabolic syndrome, FXR agonists
MeSH terms: Bile Acids and Salts, Cholesterol, Fibroblast Growth Factors, Liver, Signal Transduction, Receptors, Cytoplasmic and Nuclear

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Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

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