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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...

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Autores principales: Yang, Jinfei, Yao, Weiwei, Yang, Huihui, Shen, Yajing, Zhang, Yuanyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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