Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice

Autores
Duan, Jingjing; Wang, Zhuo; Duan, Ran; Yang, Chenxinhui; Zhao, Ruolin; Feng, Qi; Qin, Yuanyuan; Jiang, Jingwei; Gu, Shouyong; Lv, Kaiyan; Zhang, Libo; He, Bixia; Birnbaumer, Lutz; Yang, Song; Chen, Zhen; Yang, Yong
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background and Aims: Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. Approach and Results: In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Conclusions: Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.
Fil: Duan, Jingjing. China Pharmaceutical University; China
Fil: Wang, Zhuo. Nanjing University Of Traditional Chinese Medicine; China
Fil: Duan, Ran. China Pharmaceutical University; China
Fil: Yang, Chenxinhui. China Pharmaceutical University; China
Fil: Zhao, Ruolin. China Pharmaceutical University; China
Fil: Feng, Qi. China Pharmaceutical University; China
Fil: Qin, Yuanyuan. China Pharmaceutical University; China
Fil: Jiang, Jingwei. China Pharmaceutical University; China
Fil: Gu, Shouyong. Jiangsu Province Geriatric Hospital; China
Fil: Lv, Kaiyan. China Pharmaceutical University; China
Fil: Zhang, Libo. China Pharmaceutical University; China
Fil: He, Bixia. China Pharmaceutical University; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Yang, Song. Beijing Ditan Hospital Capital Medical University; China
Fil: Chen, Zhen. China Pharmaceutical University; China
Fil: Yang, Yong. China Pharmaceutical University; China
Materia
ACSL4
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/216335
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Therapeutic targeting of hepatic ACSL4 ameliorates NASH in miceDuan, JingjingWang, ZhuoDuan, RanYang, ChenxinhuiZhao, RuolinFeng, QiQin, YuanyuanJiang, JingweiGu, ShouyongLv, KaiyanZhang, LiboHe, BixiaBirnbaumer, LutzYang, SongChen, ZhenYang, YongACSL4https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background and Aims: Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. Approach and Results: In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Conclusions: Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.Fil: Duan, Jingjing. China Pharmaceutical University; ChinaFil: Wang, Zhuo. Nanjing University Of Traditional Chinese Medicine; ChinaFil: Duan, Ran. China Pharmaceutical University; ChinaFil: Yang, Chenxinhui. China Pharmaceutical University; ChinaFil: Zhao, Ruolin. China Pharmaceutical University; ChinaFil: Feng, Qi. China Pharmaceutical University; ChinaFil: Qin, Yuanyuan. China Pharmaceutical University; ChinaFil: Jiang, Jingwei. China Pharmaceutical University; ChinaFil: Gu, Shouyong. Jiangsu Province Geriatric Hospital; ChinaFil: Lv, Kaiyan. China Pharmaceutical University; ChinaFil: Zhang, Libo. China Pharmaceutical University; ChinaFil: He, Bixia. China Pharmaceutical University; ChinaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Yang, Song. Beijing Ditan Hospital Capital Medical University; ChinaFil: Chen, Zhen. China Pharmaceutical University; ChinaFil: Yang, Yong. China Pharmaceutical University; ChinaJohn Wiley & Sons2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216335Duan, Jingjing; Wang, Zhuo; Duan, Ran; Yang, Chenxinhui; Zhao, Ruolin; et al.; Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice; John Wiley & Sons; Hepatology (Baltimore, Md.); 75; 1; 1-2022; 140-1530270-9139CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/hep.32148info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:52:46Zoai:ri.conicet.gov.ar:11336/216335instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:52:46.691CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
title Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
spellingShingle Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
Duan, Jingjing
ACSL4
title_short Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
title_full Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
title_fullStr Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
title_full_unstemmed Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
title_sort Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice
dc.creator.none.fl_str_mv Duan, Jingjing
Wang, Zhuo
Duan, Ran
Yang, Chenxinhui
Zhao, Ruolin
Feng, Qi
Qin, Yuanyuan
Jiang, Jingwei
Gu, Shouyong
Lv, Kaiyan
Zhang, Libo
He, Bixia
Birnbaumer, Lutz
Yang, Song
Chen, Zhen
Yang, Yong
author Duan, Jingjing
author_facet Duan, Jingjing
Wang, Zhuo
Duan, Ran
Yang, Chenxinhui
Zhao, Ruolin
Feng, Qi
Qin, Yuanyuan
Jiang, Jingwei
Gu, Shouyong
Lv, Kaiyan
Zhang, Libo
He, Bixia
Birnbaumer, Lutz
Yang, Song
Chen, Zhen
Yang, Yong
author_role author
author2 Wang, Zhuo
Duan, Ran
Yang, Chenxinhui
Zhao, Ruolin
Feng, Qi
Qin, Yuanyuan
Jiang, Jingwei
Gu, Shouyong
Lv, Kaiyan
Zhang, Libo
He, Bixia
Birnbaumer, Lutz
Yang, Song
Chen, Zhen
Yang, Yong
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACSL4
topic ACSL4
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background and Aims: Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. Approach and Results: In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Conclusions: Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.
Fil: Duan, Jingjing. China Pharmaceutical University; China
Fil: Wang, Zhuo. Nanjing University Of Traditional Chinese Medicine; China
Fil: Duan, Ran. China Pharmaceutical University; China
Fil: Yang, Chenxinhui. China Pharmaceutical University; China
Fil: Zhao, Ruolin. China Pharmaceutical University; China
Fil: Feng, Qi. China Pharmaceutical University; China
Fil: Qin, Yuanyuan. China Pharmaceutical University; China
Fil: Jiang, Jingwei. China Pharmaceutical University; China
Fil: Gu, Shouyong. Jiangsu Province Geriatric Hospital; China
Fil: Lv, Kaiyan. China Pharmaceutical University; China
Fil: Zhang, Libo. China Pharmaceutical University; China
Fil: He, Bixia. China Pharmaceutical University; China
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Yang, Song. Beijing Ditan Hospital Capital Medical University; China
Fil: Chen, Zhen. China Pharmaceutical University; China
Fil: Yang, Yong. China Pharmaceutical University; China
description Background and Aims: Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. Approach and Results: In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Conclusions: Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/216335
Duan, Jingjing; Wang, Zhuo; Duan, Ran; Yang, Chenxinhui; Zhao, Ruolin; et al.; Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice; John Wiley & Sons; Hepatology (Baltimore, Md.); 75; 1; 1-2022; 140-153
0270-9139
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216335
identifier_str_mv Duan, Jingjing; Wang, Zhuo; Duan, Ran; Yang, Chenxinhui; Zhao, Ruolin; et al.; Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice; John Wiley & Sons; Hepatology (Baltimore, Md.); 75; 1; 1-2022; 140-153
0270-9139
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/hep.32148
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613617253613568
score 13.070432

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