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Design and synthesis of ERα agonists: Effectively reduce lipid accumulation
In recent years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing worldwide. Hepatic lipid deposition is a major feature of NAFLD, and insulin resistance is one of the most important causes of lipid deposition. Insulin resistance results in the disruption of lipid metab...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772986/ https://www.ncbi.nlm.nih.gov/pubmed/36569962 http://dx.doi.org/10.3389/fchem.2022.1104249 |
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author | Yang, Jinfei Yao, Weiwei Yang, Huihui Shen, Yajing Zhang, Yuanyuan |
author_facet | Yang, Jinfei Yao, Weiwei Yang, Huihui Shen, Yajing Zhang, Yuanyuan |
author_sort | Yang, Jinfei |
collection | PubMed |
description | In recent years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing worldwide. Hepatic lipid deposition is a major feature of NAFLD, and insulin resistance is one of the most important causes of lipid deposition. Insulin resistance results in the disruption of lipid metabolism homeostasis characterized by increased lipogenesis and decreased lipolysis. Estrogen receptor α (ERα) has been widely reported to be closely related to lipid metabolism. Activating ERa may be a promising strategy to improve lipid metabolism. Here, we used computer-aided drug design technology to discover a highly active compound, YRL-03, which can effectively reduce lipid accumulation. Cellular experimental results showed that YRL-03 could effectively reduce lipid accumulation by targeting ERα, thereby achieving alleviation of insulin resistance. We believe this study provides meaningful guidance for future molecular development of drugs to prevent and treat NAFLD. |
format | Online Article Text |
id | pubmed-9772986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97729862022-12-23 Design and synthesis of ERα agonists: Effectively reduce lipid accumulation Yang, Jinfei Yao, Weiwei Yang, Huihui Shen, Yajing Zhang, Yuanyuan Front Chem Chemistry In recent years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing worldwide. Hepatic lipid deposition is a major feature of NAFLD, and insulin resistance is one of the most important causes of lipid deposition. Insulin resistance results in the disruption of lipid metabolism homeostasis characterized by increased lipogenesis and decreased lipolysis. Estrogen receptor α (ERα) has been widely reported to be closely related to lipid metabolism. Activating ERa may be a promising strategy to improve lipid metabolism. Here, we used computer-aided drug design technology to discover a highly active compound, YRL-03, which can effectively reduce lipid accumulation. Cellular experimental results showed that YRL-03 could effectively reduce lipid accumulation by targeting ERα, thereby achieving alleviation of insulin resistance. We believe this study provides meaningful guidance for future molecular development of drugs to prevent and treat NAFLD. Frontiers Media S.A. 2022-12-08 /pmc/articles/PMC9772986/ /pubmed/36569962 http://dx.doi.org/10.3389/fchem.2022.1104249 Text en Copyright © 2022 Yang, Yao, Yang, Shen and Zhang. 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 | Chemistry Yang, Jinfei Yao, Weiwei Yang, Huihui Shen, Yajing Zhang, Yuanyuan Design and synthesis of ERα agonists: Effectively reduce lipid accumulation |
title | Design and synthesis of ERα agonists: Effectively reduce lipid accumulation |
title_full | Design and synthesis of ERα agonists: Effectively reduce lipid accumulation |
title_fullStr | Design and synthesis of ERα agonists: Effectively reduce lipid accumulation |
title_full_unstemmed | Design and synthesis of ERα agonists: Effectively reduce lipid accumulation |
title_short | Design and synthesis of ERα agonists: Effectively reduce lipid accumulation |
title_sort | design and synthesis of erα agonists: effectively reduce lipid accumulation |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772986/ https://www.ncbi.nlm.nih.gov/pubmed/36569962 http://dx.doi.org/10.3389/fchem.2022.1104249 |
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