Targeting ERK3/MK5 complex for treatment of obesity and diabetes.

Kinases represent one of the largest druggable families of proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to the development of diabetes and associated diseases. Previous results indicate that the complex between Extrace...

Descripción completa

Detalles Bibliográficos
Autores: Loza-Valdes, Angel, El-Merahbi, Rabih, Kassouf, Toufic, Demczuk, Agnieszka, Reuter, Saskia, Viera, Jonathan Trujillo, Karwen, Till, Noh, Minhe, Löffler, Mona C, Romero-Becerra, Rafael, Torres, Jorge L, Marcos, Miguel, Sabio, Guadalupe, Wojda, Urszula, Sumara, Grzegorz
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15738
Acceso en línea:http://hdl.handle.net/20.500.12105/15738
Access Level:acceso abierto
Palabra clave:Diabetes Mellitus
Protein Serine-Threonine Kinases
Animals
id ES_f7a9be1d19ea5a0f308ea3348c30874e
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/15738
network_acronym_str ES
network_name_str España
repository_id_str
spelling Targeting ERK3/MK5 complex for treatment of obesity and diabetes.Loza-Valdes, AngelEl-Merahbi, RabihKassouf, TouficDemczuk, AgnieszkaReuter, SaskiaViera, Jonathan TrujilloKarwen, TillNoh, MinheLöffler, Mona CRomero-Becerra, RafaelTorres, Jorge LMarcos, MiguelSabio, GuadalupeWojda, UrszulaSumara, GrzegorzDiabetes MellitusProtein Serine-Threonine KinasesAnimalsKinases represent one of the largest druggable families of proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to the development of diabetes and associated diseases. Previous results indicate that the complex between Extracellular-regulated kinase 3 (ERK3) and Mitogen-Activated Protein Kinase (MAPK)-activated protein kinase 5 (MK5) suppresses energy dissipation and promotes fatty acids (FAs) output in adipose tissue and, therefore promotes obesity and diabetes. However, the therapeutic potential of targeting this complex at the systemic level has not been fully explored. Here we applied a translational approach to target the ERK3/MK5 complex in mice. Importantly, deletion of ERK3 in the whole body or administration of MK5-specific inhibitor protects against obesity and promotes insulin sensitivity. Finally, we show that the expression of ERK3 and MK5 correlates with the degree of obesity and that ERK3/MK5 complex regulates energy dissipation in human adipocytes. Altogether, we demonstrate that ERK3/MK5 complex can be targeted in vivo to preserve metabolic health and combat obesity and diabetes.ElsevierUnión Europea. Comisión Europea. European Research Council (ERC)European Molecular Biology OrganizationMax Planck Society20232023-04-0320222022-07-0520222022-07-05journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/15738reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme ERCEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme Su820European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 2020 Eopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/157382026-06-12T12:43:37Z
dc.title.none.fl_str_mv Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
title Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
spellingShingle Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
Loza-Valdes, Angel
Diabetes Mellitus
Protein Serine-Threonine Kinases
Animals
title_short Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
title_full Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
title_fullStr Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
title_full_unstemmed Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
title_sort Targeting ERK3/MK5 complex for treatment of obesity and diabetes.
dc.creator.none.fl_str_mv Loza-Valdes, Angel
El-Merahbi, Rabih
Kassouf, Toufic
Demczuk, Agnieszka
Reuter, Saskia
Viera, Jonathan Trujillo
Karwen, Till
Noh, Minhe
Löffler, Mona C
Romero-Becerra, Rafael
Torres, Jorge L
Marcos, Miguel
Sabio, Guadalupe
Wojda, Urszula
Sumara, Grzegorz
author Loza-Valdes, Angel
author_facet Loza-Valdes, Angel
El-Merahbi, Rabih
Kassouf, Toufic
Demczuk, Agnieszka
Reuter, Saskia
Viera, Jonathan Trujillo
Karwen, Till
Noh, Minhe
Löffler, Mona C
Romero-Becerra, Rafael
Torres, Jorge L
Marcos, Miguel
Sabio, Guadalupe
Wojda, Urszula
Sumara, Grzegorz
author_role author
author2 El-Merahbi, Rabih
Kassouf, Toufic
Demczuk, Agnieszka
Reuter, Saskia
Viera, Jonathan Trujillo
Karwen, Till
Noh, Minhe
Löffler, Mona C
Romero-Becerra, Rafael
Torres, Jorge L
Marcos, Miguel
Sabio, Guadalupe
Wojda, Urszula
Sumara, Grzegorz
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Unión Europea. Comisión Europea. European Research Council (ERC)
European Molecular Biology Organization
Max Planck Society
dc.subject.none.fl_str_mv Diabetes Mellitus
Protein Serine-Threonine Kinases
Animals
topic Diabetes Mellitus
Protein Serine-Threonine Kinases
Animals
description Kinases represent one of the largest druggable families of proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to the development of diabetes and associated diseases. Previous results indicate that the complex between Extracellular-regulated kinase 3 (ERK3) and Mitogen-Activated Protein Kinase (MAPK)-activated protein kinase 5 (MK5) suppresses energy dissipation and promotes fatty acids (FAs) output in adipose tissue and, therefore promotes obesity and diabetes. However, the therapeutic potential of targeting this complex at the systemic level has not been fully explored. Here we applied a translational approach to target the ERK3/MK5 complex in mice. Importantly, deletion of ERK3 in the whole body or administration of MK5-specific inhibitor protects against obesity and promotes insulin sensitivity. Finally, we show that the expression of ERK3 and MK5 correlates with the degree of obesity and that ERK3/MK5 complex regulates energy dissipation in human adipocytes. Altogether, we demonstrate that ERK3/MK5 complex can be targeted in vivo to preserve metabolic health and combat obesity and diabetes.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-07-05
2022
2022-07-05
2023
2023-04-03
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/15738
url http://hdl.handle.net/20.500.12105/15738
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme ERC
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme Su820
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 2020 E
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424903560626176
score 15,811543

Similares en LA Referencia