Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases

Cardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the...

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Autores: López-Yoldi, Miguel, Fernández-Galilea, Marta, Laiglesia, Laura M., Larequi, Eduardo, Prieto, Jesús, Martínez, J Alfredo, Bustos, Matilde, Moreno-Aliaga, Maria Jesús
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2014
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/415216
Acesso em linha:http://hdl.handle.net/10261/415216
https://api.elsevier.com/content/abstract/scopus_id/84919770352
Access Level:Acceso aberto
Palavra-chave:Adipocytes
Adipose triglyceride lipase
Cell signaling
Cytokines
Hormone-sensitive lipase
Oobesity
Perilipin
Protein kinase A
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spelling Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipasesLópez-Yoldi, MiguelFernández-Galilea, MartaLaiglesia, Laura M.Larequi, EduardoPrieto, JesúsMartínez, J AlfredoBustos, MatildeMoreno-Aliaga, Maria JesúsAdipocytesAdipose triglyceride lipaseCell signalingCytokinesHormone-sensitive lipaseOobesityPerilipinProtein kinase ACardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the main proteins and signaling pathways involved in the regulation of lipolysis were evaluated in 3T3-L1 adipocytes and in mice. rCT-1 treatment stimulated basal glycerol release in a concentration- and time-dependent manner in 3T3-L1 adipocytes. rCT-1 (20 ng/ml for 24 h) raised cAMP levels, and in parallel increased protein kinase (PK)A-mediated phosphorylation of perilipin and hormone sensitive lipase (HSL) at Ser660. siRNA knock-down of HSL or PKA, as well as pretreatment with the PKA inhibitor H89, blunted the CT-1-induced lipolysis, suggesting that the lipolytic action of CT-1 in adipocytes is mainly mediated by activation of HSL through the PKA pathway. In ob/ob mice, acute rCT-1 treatment also promoted PKA-mediated phosphorylation of perilipin and HSL at Ser660 and Ser563, and increased adipose triglyceride lipase (desnutrin) content in adipose tissue. These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects.This study was supported by grants from the Government of Navarra (Department of Health); Mutua Madrileña Foundation; FIS (PI10/01516 and PI13/01851); Línea Especial “Nutrición, Obesidad y Salud Universidad de Navarra” and by the agreement between FIMA and the “UTE project CIMA”. M.L-Y. was supported by a doctoral grant from Asociación de Amigos University of Navarra.Peer reviewedElsevierAmerican Society for Biochemistry and Molecular BiologyDiputación Foral de NavarraFundación Mutua MadrileñaUniversidad de NavarraAsociación de Amigos de la Universidad de NavarraMinisterio de Ciencia, Innovación y Universidades (España)Ministerio de Economía y Competitividad (España)Bustos, Matilde [0000-0003-2306-9548]202620262014info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/415216https://api.elsevier.com/content/abstract/scopus_id/84919770352reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MICINN//10%2F01516info:eu-repo/grantAgreement/MINECO//PI13%2F01851https://doi.org/10.1194/jlr.M055335Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4152162026-05-22T06:33:51Z
dc.title.none.fl_str_mv Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
title Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
spellingShingle Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
López-Yoldi, Miguel
Adipocytes
Adipose triglyceride lipase
Cell signaling
Cytokines
Hormone-sensitive lipase
Oobesity
Perilipin
Protein kinase A
title_short Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
title_full Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
title_fullStr Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
title_full_unstemmed Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
title_sort Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases
dc.creator.none.fl_str_mv López-Yoldi, Miguel
Fernández-Galilea, Marta
Laiglesia, Laura M.
Larequi, Eduardo
Prieto, Jesús
Martínez, J Alfredo
Bustos, Matilde
Moreno-Aliaga, Maria Jesús
author López-Yoldi, Miguel
author_facet López-Yoldi, Miguel
Fernández-Galilea, Marta
Laiglesia, Laura M.
Larequi, Eduardo
Prieto, Jesús
Martínez, J Alfredo
Bustos, Matilde
Moreno-Aliaga, Maria Jesús
author_role author
author2 Fernández-Galilea, Marta
Laiglesia, Laura M.
Larequi, Eduardo
Prieto, Jesús
Martínez, J Alfredo
Bustos, Matilde
Moreno-Aliaga, Maria Jesús
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Diputación Foral de Navarra
Fundación Mutua Madrileña
Universidad de Navarra
Asociación de Amigos de la Universidad de Navarra
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Economía y Competitividad (España)
Bustos, Matilde [0000-0003-2306-9548]
dc.subject.none.fl_str_mv Adipocytes
Adipose triglyceride lipase
Cell signaling
Cytokines
Hormone-sensitive lipase
Oobesity
Perilipin
Protein kinase A
topic Adipocytes
Adipose triglyceride lipase
Cell signaling
Cytokines
Hormone-sensitive lipase
Oobesity
Perilipin
Protein kinase A
description Cardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the main proteins and signaling pathways involved in the regulation of lipolysis were evaluated in 3T3-L1 adipocytes and in mice. rCT-1 treatment stimulated basal glycerol release in a concentration- and time-dependent manner in 3T3-L1 adipocytes. rCT-1 (20 ng/ml for 24 h) raised cAMP levels, and in parallel increased protein kinase (PK)A-mediated phosphorylation of perilipin and hormone sensitive lipase (HSL) at Ser660. siRNA knock-down of HSL or PKA, as well as pretreatment with the PKA inhibitor H89, blunted the CT-1-induced lipolysis, suggesting that the lipolytic action of CT-1 in adipocytes is mainly mediated by activation of HSL through the PKA pathway. In ob/ob mice, acute rCT-1 treatment also promoted PKA-mediated phosphorylation of perilipin and HSL at Ser660 and Ser563, and increased adipose triglyceride lipase (desnutrin) content in adipose tissue. These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects.
publishDate 2014
dc.date.none.fl_str_mv 2014
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/415216
https://api.elsevier.com/content/abstract/scopus_id/84919770352
url http://hdl.handle.net/10261/415216
https://api.elsevier.com/content/abstract/scopus_id/84919770352
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MICINN//10%2F01516
info:eu-repo/grantAgreement/MINECO//PI13%2F01851
https://doi.org/10.1194/jlr.M055335
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv Elsevier
American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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