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

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...

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Detalles Bibliográficos
Autores principales: Katafuchi, Takeshi, Makishima, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181207/
https://www.ncbi.nlm.nih.gov/pubmed/35682726
http://dx.doi.org/10.3390/ijms23116046
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author Katafuchi, Takeshi
Makishima, Makoto
author_facet Katafuchi, Takeshi
Makishima, Makoto
author_sort Katafuchi, Takeshi
collection PubMed
description 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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spelling pubmed-91812072022-06-10 Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis Katafuchi, Takeshi Makishima, Makoto Int J Mol Sci Review 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. MDPI 2022-05-27 /pmc/articles/PMC9181207/ /pubmed/35682726 http://dx.doi.org/10.3390/ijms23116046 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Katafuchi, Takeshi
Makishima, Makoto
Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
title Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
title_full Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
title_fullStr Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
title_full_unstemmed Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
title_short Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
title_sort molecular basis of bile acid-fxr-fgf15/19 signaling axis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181207/
https://www.ncbi.nlm.nih.gov/pubmed/35682726
http://dx.doi.org/10.3390/ijms23116046
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