PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury

Ischemia-reperfusion injury (IRI) remains a frequent complication in surgery, especially in case of steatotic livers that present decreased tolerance towards IRI. Apart from its major role in metabolism, activation of peroxisome proliferator-activated receptor α (PPARα) has been related with positiv...

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Autores: Pantazi, Eirini, Folch-Puy, Emma, Bejaoui, Mohamed, Panisello-Roselló, Arnau, Varela, Ana Teresa, Rolo, Anabela Pinto, Palmeira, Carlos M., Roselló-Catafau, Joan
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/148515
Acesso em linha:http://hdl.handle.net/10261/148515
Access Level:acceso abierto
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spelling PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion InjuryPantazi, EiriniFolch-Puy, EmmaBejaoui, MohamedPanisello-Roselló, ArnauVarela, Ana TeresaRolo, Anabela PintoPalmeira, Carlos M.Roselló-Catafau, JoanIschemia-reperfusion injury (IRI) remains a frequent complication in surgery, especially in case of steatotic livers that present decreased tolerance towards IRI. Apart from its major role in metabolism, activation of peroxisome proliferator-activated receptor α (PPARα) has been related with positive effects on IRI. In addition, the deacetylase enzyme sirtuin 1 (SIRT1) has recently emerged as a promising target for preventing IRI, through its interaction with stress-related mechanisms, such as endoplasmic reticulum stress (ERS). Taking this into account, this study aims to explore whether PPARα agonist WY-14643 could protect steatotic livers against IRI through sirtuins and ERS signaling pathway. Obese Zucker rats were pretreated or not pretreated with WY-14643 (10 mg/kg intravenously) and then submitted to partial (70%) hepatic ischemia (1 hour) followed by 24 hours of reperfusion. Liver injury (ALT levels), lipid peroxidation (MDA), SIRT1 activity, and the protein expression of SIRT1 and SIRT3 and ERS parameters (IRE1α, peIF2, caspase 12, and CHOP) were evaluated. Treatment with WY-14643 reduced liver injury in fatty livers, enhanced SIRT1 activity, and prevented ERS. Together, our results indicated that PPARα agonist WY-14643 may exert its protective effect in fatty livers, at least in part, via SIRT1 induction and ERS prevention.Eirini Pantazi thanks the fellowship from AGAUR (2012FI_B00382), Generalitat de Catalunya, Barcelona, Catalonia, Spain. The authors would like to thank the Fondo de Investigaciones Sanitarias (FIS PI12/00519) for the economic support.Peer ReviewedHindawi Publishing CorporationInstituto de Salud Carlos IIIGeneralitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720152017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/148515reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1155/2015/894679Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1485152026-05-22T06:33:51Z
dc.title.none.fl_str_mv PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
title PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
spellingShingle PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
Pantazi, Eirini
title_short PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
title_full PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
title_fullStr PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
title_full_unstemmed PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
title_sort PPAR α Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
dc.creator.none.fl_str_mv Pantazi, Eirini
Folch-Puy, Emma
Bejaoui, Mohamed
Panisello-Roselló, Arnau
Varela, Ana Teresa
Rolo, Anabela Pinto
Palmeira, Carlos M.
Roselló-Catafau, Joan
author Pantazi, Eirini
author_facet Pantazi, Eirini
Folch-Puy, Emma
Bejaoui, Mohamed
Panisello-Roselló, Arnau
Varela, Ana Teresa
Rolo, Anabela Pinto
Palmeira, Carlos M.
Roselló-Catafau, Joan
author_role author
author2 Folch-Puy, Emma
Bejaoui, Mohamed
Panisello-Roselló, Arnau
Varela, Ana Teresa
Rolo, Anabela Pinto
Palmeira, Carlos M.
Roselló-Catafau, Joan
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Ischemia-reperfusion injury (IRI) remains a frequent complication in surgery, especially in case of steatotic livers that present decreased tolerance towards IRI. Apart from its major role in metabolism, activation of peroxisome proliferator-activated receptor α (PPARα) has been related with positive effects on IRI. In addition, the deacetylase enzyme sirtuin 1 (SIRT1) has recently emerged as a promising target for preventing IRI, through its interaction with stress-related mechanisms, such as endoplasmic reticulum stress (ERS). Taking this into account, this study aims to explore whether PPARα agonist WY-14643 could protect steatotic livers against IRI through sirtuins and ERS signaling pathway. Obese Zucker rats were pretreated or not pretreated with WY-14643 (10 mg/kg intravenously) and then submitted to partial (70%) hepatic ischemia (1 hour) followed by 24 hours of reperfusion. Liver injury (ALT levels), lipid peroxidation (MDA), SIRT1 activity, and the protein expression of SIRT1 and SIRT3 and ERS parameters (IRE1α, peIF2, caspase 12, and CHOP) were evaluated. Treatment with WY-14643 reduced liver injury in fatty livers, enhanced SIRT1 activity, and prevented ERS. Together, our results indicated that PPARα agonist WY-14643 may exert its protective effect in fatty livers, at least in part, via SIRT1 induction and ERS prevention.
publishDate 2015
dc.date.none.fl_str_mv 2015
2017
2017
2017
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/10261/148515
url http://hdl.handle.net/10261/148515
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1155/2015/894679
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Hindawi Publishing Corporation
publisher.none.fl_str_mv Hindawi Publishing Corporation
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 15.812429

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