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Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders

The Farnesoid X receptor (FXR) is a nuclear receptor which is activated by bile acids. Bile acids function in solubilization of dietary fats and vitamins in the intestine. In addition, bile acids have been increasingly recognized to act as signaling molecules involved in energy metabolism pathways,...

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Autores principales: Appelman, Monique D., van der Veen, Suzanne W., van Mil, Saskia W. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503269/
https://www.ncbi.nlm.nih.gov/pubmed/34646233
http://dx.doi.org/10.3389/fendo.2021.729828
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author Appelman, Monique D.
van der Veen, Suzanne W.
van Mil, Saskia W. C.
author_facet Appelman, Monique D.
van der Veen, Suzanne W.
van Mil, Saskia W. C.
author_sort Appelman, Monique D.
collection PubMed
description The Farnesoid X receptor (FXR) is a nuclear receptor which is activated by bile acids. Bile acids function in solubilization of dietary fats and vitamins in the intestine. In addition, bile acids have been increasingly recognized to act as signaling molecules involved in energy metabolism pathways, amongst others via activating FXR. Upon activation by bile acids, FXR controls the expression of many genes involved in bile acid, lipid, glucose and amino acid metabolism. An inability to properly use and store energy substrates may predispose to metabolic disorders, such as obesity, diabetes, cholestasis and non-alcoholic fatty liver disease. These diseases arise through a complex interplay between genetics, environment and nutrition. Due to its function in metabolism, FXR is an attractive treatment target for these disorders. The regulation of FXR expression and activity occurs both at the transcriptional and at the post-transcriptional level. It has been shown that FXR can be phosphorylated, SUMOylated and acetylated, amongst other modifications, and that these modifications have functional consequences for DNA and ligand binding, heterodimerization and subcellular localization of FXR. In addition, these post-translational modifications may selectively increase or decrease transcription of certain target genes. In this review, we provide an overview of the posttranslational modifications of FXR and discuss their potential involvement in cholestatic and metabolic disorders.
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spelling pubmed-85032692021-10-12 Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders Appelman, Monique D. van der Veen, Suzanne W. van Mil, Saskia W. C. Front Endocrinol (Lausanne) Endocrinology The Farnesoid X receptor (FXR) is a nuclear receptor which is activated by bile acids. Bile acids function in solubilization of dietary fats and vitamins in the intestine. In addition, bile acids have been increasingly recognized to act as signaling molecules involved in energy metabolism pathways, amongst others via activating FXR. Upon activation by bile acids, FXR controls the expression of many genes involved in bile acid, lipid, glucose and amino acid metabolism. An inability to properly use and store energy substrates may predispose to metabolic disorders, such as obesity, diabetes, cholestasis and non-alcoholic fatty liver disease. These diseases arise through a complex interplay between genetics, environment and nutrition. Due to its function in metabolism, FXR is an attractive treatment target for these disorders. The regulation of FXR expression and activity occurs both at the transcriptional and at the post-transcriptional level. It has been shown that FXR can be phosphorylated, SUMOylated and acetylated, amongst other modifications, and that these modifications have functional consequences for DNA and ligand binding, heterodimerization and subcellular localization of FXR. In addition, these post-translational modifications may selectively increase or decrease transcription of certain target genes. In this review, we provide an overview of the posttranslational modifications of FXR and discuss their potential involvement in cholestatic and metabolic disorders. Frontiers Media S.A. 2021-09-27 /pmc/articles/PMC8503269/ /pubmed/34646233 http://dx.doi.org/10.3389/fendo.2021.729828 Text en Copyright © 2021 Appelman, van der Veen and van Mil https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Appelman, Monique D.
van der Veen, Suzanne W.
van Mil, Saskia W. C.
Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
title Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
title_full Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
title_fullStr Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
title_full_unstemmed Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
title_short Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
title_sort post-translational modifications of fxr; implications for cholestasis and obesity-related disorders
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503269/
https://www.ncbi.nlm.nih.gov/pubmed/34646233
http://dx.doi.org/10.3389/fendo.2021.729828
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