Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity

Adipogenesis is the process of differentiation of immature mesenchymal stem cells into adipocytes. Elucidation of the mechanisms that regulate adipocyte differentiation is key for the development of novel therapies for the control of obesity and related comorbidities. Cytosolic group IVA phospholipa...

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Autores: Peña, Lucía, Meana, Clara, Astudillo, Alma M., Lordén, Gema, Valdearcos, Martín, Sato, Hiroyasu, Murakami, Makoto, Balsinde, Jesús, Balboa, María A.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/157925
Acceso en línea:http://hdl.handle.net/10261/157925
Access Level:acceso abierto
Palabra clave:Phospholipase A2
Obesity
Adipocytes
Arachidonic acid
Adipogenesis
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spelling Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesityPeña, LucíaMeana, ClaraAstudillo, Alma M.Lordén, GemaValdearcos, MartínSato, HiroyasuMurakami, MakotoBalsinde, JesúsBalboa, María A.Phospholipase A2ObesityAdipocytesArachidonic acidAdipogenesisAdipogenesis is the process of differentiation of immature mesenchymal stem cells into adipocytes. Elucidation of the mechanisms that regulate adipocyte differentiation is key for the development of novel therapies for the control of obesity and related comorbidities. Cytosolic group IVA phospholipase A (cPLAα) is the pivotal enzyme in receptor-mediated arachidonic acid (AA) mobilization and attendant eicosanoid production. Using primary multipotent cells and cell lines predetermined to become adipocytes, we show here that cPLAα displays a proadipogenic function that occurs very early in the adipogenic process. Interestingly, cPLAα levels decrease during adipogenesis, but cPLAα-deficient preadipocytes exhibit a reduced capacity to differentiate into adipocytes, which affects early and terminal adipogenic transcription factors. Additionally, the absence of the phospholipase alters proliferation and cell-cycle progression that takes place during adipogenesis. Preconditioning of preadipocytes with AA increases the adipogenic capacity of these cells. Moreover, animals deficient in cPLAα show resistance to obesity when fed a high fat diet that parallels changes in the expression of adipogenic transcription factors of the adipose tissue. Collectively, these results show that preadipocyte cPLAα activation is a hitherto unrecognized factor for adipogenesis in vitro and in vivo.This work was supported by the Spanish Ministry of Science and Innovation (Grants SAF2010-18831, BFU2010-18826 and SAF2013-48201-R), the Regional Government of Castile and Leon (Grants BIO39/VA04/10, CSI168A12-1 and BIO/VA03/14) and by grants-in aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and AMED-CREST from the Japan Agency for Medical Research and Development (MM and HS). L.P. and G.L. were supported by predoctoral fellowships from the Spanish Ministry of Science and Innovation (Plan de Formación de Personal Investigador and Plan de Formación de Profesorado Universitario programs, respectively). M.V. was supported by a predoctoral fellowship from the Regional Government of Castile and Leon. CIBERDEM is an initiative of Instituto de Salud Carlos III.Peer ReviewedElsevierInstituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)Ministerio de Economía y Competitividad (España)Ministry of Education, Culture, Sports, Science and Technology (Japan)Junta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720162017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/157925reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48201-Rhttps://doi.org/10.1016/j.bbalip.2016.06.004Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1579252026-05-22T06:33:51Z
dc.title.none.fl_str_mv Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
title Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
spellingShingle Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
Peña, Lucía
Phospholipase A2
Obesity
Adipocytes
Arachidonic acid
Adipogenesis
title_short Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
title_full Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
title_fullStr Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
title_full_unstemmed Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
title_sort Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity
dc.creator.none.fl_str_mv Peña, Lucía
Meana, Clara
Astudillo, Alma M.
Lordén, Gema
Valdearcos, Martín
Sato, Hiroyasu
Murakami, Makoto
Balsinde, Jesús
Balboa, María A.
author Peña, Lucía
author_facet Peña, Lucía
Meana, Clara
Astudillo, Alma M.
Lordén, Gema
Valdearcos, Martín
Sato, Hiroyasu
Murakami, Makoto
Balsinde, Jesús
Balboa, María A.
author_role author
author2 Meana, Clara
Astudillo, Alma M.
Lordén, Gema
Valdearcos, Martín
Sato, Hiroyasu
Murakami, Makoto
Balsinde, Jesús
Balboa, María A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
Ministerio de Economía y Competitividad (España)
Ministry of Education, Culture, Sports, Science and Technology (Japan)
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Phospholipase A2
Obesity
Adipocytes
Arachidonic acid
Adipogenesis
topic Phospholipase A2
Obesity
Adipocytes
Arachidonic acid
Adipogenesis
description Adipogenesis is the process of differentiation of immature mesenchymal stem cells into adipocytes. Elucidation of the mechanisms that regulate adipocyte differentiation is key for the development of novel therapies for the control of obesity and related comorbidities. Cytosolic group IVA phospholipase A (cPLAα) is the pivotal enzyme in receptor-mediated arachidonic acid (AA) mobilization and attendant eicosanoid production. Using primary multipotent cells and cell lines predetermined to become adipocytes, we show here that cPLAα displays a proadipogenic function that occurs very early in the adipogenic process. Interestingly, cPLAα levels decrease during adipogenesis, but cPLAα-deficient preadipocytes exhibit a reduced capacity to differentiate into adipocytes, which affects early and terminal adipogenic transcription factors. Additionally, the absence of the phospholipase alters proliferation and cell-cycle progression that takes place during adipogenesis. Preconditioning of preadipocytes with AA increases the adipogenic capacity of these cells. Moreover, animals deficient in cPLAα show resistance to obesity when fed a high fat diet that parallels changes in the expression of adipogenic transcription factors of the adipose tissue. Collectively, these results show that preadipocyte cPLAα activation is a hitherto unrecognized factor for adipogenesis in vitro and in vivo.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/157925
url http://hdl.handle.net/10261/157925
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48201-R
https://doi.org/10.1016/j.bbalip.2016.06.004
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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score 15,811543

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