Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases

Detalhes bibliográficos
Autor(a) principal: Sousa-Lima, Inês
Data de Publicação: 2021
Outros Autores: Kim, Hyun Jeong, Jones, John, Kim, Young-Bum
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/103849
https://doi.org/10.4093/dmj.2021.0197
Resumo: Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.
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spelling Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver DiseasesRho-kinaseAMP-activated protein kinaseDiet, high-fatLipogenesisNonalcoholic fatty liver diseaseAnimalsLipogenesisMicerho-Associated KinasesDiabetes Mellitus, Type 2Non-alcoholic Fatty Liver DiseaseNonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.Korean Diabetes Association2021-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103849http://hdl.handle.net/10316/103849https://doi.org/10.4093/dmj.2021.0197eng2233-60792233-6087Sousa-Lima, InêsKim, Hyun JeongJones, JohnKim, Young-Buminfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-12-02T21:37:17Zoai:estudogeral.uc.pt:10316/103849Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:37.148901Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
title Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
spellingShingle Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
Sousa-Lima, Inês
Rho-kinase
AMP-activated protein kinase
Diet, high-fat
Lipogenesis
Nonalcoholic fatty liver disease
Animals
Lipogenesis
Mice
rho-Associated Kinases
Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease
title_short Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
title_full Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
title_fullStr Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
title_full_unstemmed Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
title_sort Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases
author Sousa-Lima, Inês
author_facet Sousa-Lima, Inês
Kim, Hyun Jeong
Jones, John
Kim, Young-Bum
author_role author
author2 Kim, Hyun Jeong
Jones, John
Kim, Young-Bum
author2_role author
author
author
dc.contributor.author.fl_str_mv Sousa-Lima, Inês
Kim, Hyun Jeong
Jones, John
Kim, Young-Bum
dc.subject.por.fl_str_mv Rho-kinase
AMP-activated protein kinase
Diet, high-fat
Lipogenesis
Nonalcoholic fatty liver disease
Animals
Lipogenesis
Mice
rho-Associated Kinases
Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease
topic Rho-kinase
AMP-activated protein kinase
Diet, high-fat
Lipogenesis
Nonalcoholic fatty liver disease
Animals
Lipogenesis
Mice
rho-Associated Kinases
Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease
description Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.
publishDate 2021
dc.date.none.fl_str_mv 2021-09
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/103849
http://hdl.handle.net/10316/103849
https://doi.org/10.4093/dmj.2021.0197
url http://hdl.handle.net/10316/103849
https://doi.org/10.4093/dmj.2021.0197
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2233-6079
2233-6087
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Korean Diabetes Association
publisher.none.fl_str_mv Korean Diabetes Association
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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