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PPARα: A potential therapeutic target of cholestasis
The accumulation of bile acids in the liver leads to the development of cholestasis and hepatocyte injury. Nuclear receptors control the synthesis and transport of bile acids in the liver. Among them, the farnesoid X receptor (FXR) is the most common receptor studied in treating cholestasis. The act...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342652/ https://www.ncbi.nlm.nih.gov/pubmed/35924060 http://dx.doi.org/10.3389/fphar.2022.916866 |
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author | Ye, Xiaoyin Zhang, Tong Han, Han |
author_facet | Ye, Xiaoyin Zhang, Tong Han, Han |
author_sort | Ye, Xiaoyin |
collection | PubMed |
description | The accumulation of bile acids in the liver leads to the development of cholestasis and hepatocyte injury. Nuclear receptors control the synthesis and transport of bile acids in the liver. Among them, the farnesoid X receptor (FXR) is the most common receptor studied in treating cholestasis. The activation of this receptor can reduce the amount of bile acid synthesis and decrease the bile acid content in the liver, alleviating cholestasis. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) have a FXR excitatory effect, but the unresponsiveness of some patients and the side effect of pruritus seriously affect the results of UDCA or OCA treatment. The activator of peroxisome proliferator-activated receptor alpha (PPARα) has emerged as a new target for controlling the synthesis and transport of bile acids during cholestasis. Moreover, the anti-inflammatory effect of PPARα can effectively reduce cholestatic liver injury, thereby improving patients’ physiological status. Here, we will focus on the function of PPARα and its involvement in the regulation of bile acid transport and metabolism. In addition, the anti-inflammatory effects of PPARα will be discussed in some detail. Finally, we will discuss the application of PPARα agonists for cholestatic liver disorders. |
format | Online Article Text |
id | pubmed-9342652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93426522022-08-02 PPARα: A potential therapeutic target of cholestasis Ye, Xiaoyin Zhang, Tong Han, Han Front Pharmacol Pharmacology The accumulation of bile acids in the liver leads to the development of cholestasis and hepatocyte injury. Nuclear receptors control the synthesis and transport of bile acids in the liver. Among them, the farnesoid X receptor (FXR) is the most common receptor studied in treating cholestasis. The activation of this receptor can reduce the amount of bile acid synthesis and decrease the bile acid content in the liver, alleviating cholestasis. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) have a FXR excitatory effect, but the unresponsiveness of some patients and the side effect of pruritus seriously affect the results of UDCA or OCA treatment. The activator of peroxisome proliferator-activated receptor alpha (PPARα) has emerged as a new target for controlling the synthesis and transport of bile acids during cholestasis. Moreover, the anti-inflammatory effect of PPARα can effectively reduce cholestatic liver injury, thereby improving patients’ physiological status. Here, we will focus on the function of PPARα and its involvement in the regulation of bile acid transport and metabolism. In addition, the anti-inflammatory effects of PPARα will be discussed in some detail. Finally, we will discuss the application of PPARα agonists for cholestatic liver disorders. Frontiers Media S.A. 2022-07-18 /pmc/articles/PMC9342652/ /pubmed/35924060 http://dx.doi.org/10.3389/fphar.2022.916866 Text en Copyright © 2022 Ye, Zhang and Han. 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 | Pharmacology Ye, Xiaoyin Zhang, Tong Han, Han PPARα: A potential therapeutic target of cholestasis |
title | PPARα: A potential therapeutic target of cholestasis |
title_full | PPARα: A potential therapeutic target of cholestasis |
title_fullStr | PPARα: A potential therapeutic target of cholestasis |
title_full_unstemmed | PPARα: A potential therapeutic target of cholestasis |
title_short | PPARα: A potential therapeutic target of cholestasis |
title_sort | pparα: a potential therapeutic target of cholestasis |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342652/ https://www.ncbi.nlm.nih.gov/pubmed/35924060 http://dx.doi.org/10.3389/fphar.2022.916866 |
work_keys_str_mv | AT yexiaoyin pparaapotentialtherapeutictargetofcholestasis AT zhangtong pparaapotentialtherapeutictargetofcholestasis AT hanhan pparaapotentialtherapeutictargetofcholestasis |