Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response

Autores
Actis Dato, Virginia; Benitez Amaro, Aleyda; Garcia, Eduardo; Claudi, Lene; LaChica Lhoëst, Maria Teresa; Iborra, Antoni; Escola Gil, Joan Carles; Guerra, Jose Maria; Samouillan, Valerie; Enrich, Carlos; Chiabrando, Gustavo Alberto; Llorente Cortés, Vicenta
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups. Findings: HFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum.
Fil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Benitez Amaro, Aleyda. Consejo Superior de Investigaciones Científicas; España
Fil: Garcia, Eduardo. Consejo Superior de Investigaciones Científicas; España
Fil: Claudi, Lene. Consejo Superior de Investigaciones Científicas; España
Fil: LaChica Lhoëst, Maria Teresa. Consejo Superior de Investigaciones Científicas; España
Fil: Iborra, Antoni. Universitat Autònoma de Barcelona; España
Fil: Escola Gil, Joan Carles. Consejo Superior de Investigaciones Científicas; España
Fil: Guerra, Jose Maria. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Samouillan, Valerie. Université Paul Sabatier; Francia
Fil: Enrich, Carlos. INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS); . Universidad de Barcelona; España
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Llorente Cortés, Vicenta. Consejo Superior de Investigaciones Científicas; España
Materia
CHOLESTERYL ESTERS
HEART
HIGH-FAT DIET
INSULIN
LIPID DROPLETS
LIPOPROTEIN
LRP1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/216879
Acceder
id CONICETDig_e9b3e694d49e09ed3b92d89a2a6cf2a7
oai_identifier_str oai:ri.conicet.gov.ar:11336/216879
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Targeting cholesteryl ester accumulation in the heart improves cardiac insulin responseActis Dato, VirginiaBenitez Amaro, AleydaGarcia, EduardoClaudi, LeneLaChica Lhoëst, Maria TeresaIborra, AntoniEscola Gil, Joan CarlesGuerra, Jose MariaSamouillan, ValerieEnrich, CarlosChiabrando, Gustavo AlbertoLlorente Cortés, VicentaCHOLESTERYL ESTERSHEARTHIGH-FAT DIETINSULINLIPID DROPLETSLIPOPROTEINLRP1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups. Findings: HFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum.Fil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Benitez Amaro, Aleyda. Consejo Superior de Investigaciones Científicas; EspañaFil: Garcia, Eduardo. Consejo Superior de Investigaciones Científicas; EspañaFil: Claudi, Lene. Consejo Superior de Investigaciones Científicas; EspañaFil: LaChica Lhoëst, Maria Teresa. Consejo Superior de Investigaciones Científicas; EspañaFil: Iborra, Antoni. Universitat Autònoma de Barcelona; EspañaFil: Escola Gil, Joan Carles. Consejo Superior de Investigaciones Científicas; EspañaFil: Guerra, Jose Maria. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; EspañaFil: Samouillan, Valerie. Université Paul Sabatier; FranciaFil: Enrich, Carlos. INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS); . Universidad de Barcelona; EspañaFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Llorente Cortés, Vicenta. Consejo Superior de Investigaciones Científicas; EspañaElsevier France-Editions Scientifiques Medicales Elsevier2022-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216879Actis Dato, Virginia; Benitez Amaro, Aleyda; Garcia, Eduardo; Claudi, Lene; LaChica Lhoëst, Maria Teresa; et al.; Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response; Elsevier France-Editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 152; 6-2022; 1-140753-3322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2022.113270info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:01Zoai:ri.conicet.gov.ar:11336/216879instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:01.437CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
title Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
spellingShingle Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
Actis Dato, Virginia
CHOLESTERYL ESTERS
HEART
HIGH-FAT DIET
INSULIN
LIPID DROPLETS
LIPOPROTEIN
LRP1
title_short Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
title_full Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
title_fullStr Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
title_full_unstemmed Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
title_sort Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response
dc.creator.none.fl_str_mv Actis Dato, Virginia
Benitez Amaro, Aleyda
Garcia, Eduardo
Claudi, Lene
LaChica Lhoëst, Maria Teresa
Iborra, Antoni
Escola Gil, Joan Carles
Guerra, Jose Maria
Samouillan, Valerie
Enrich, Carlos
Chiabrando, Gustavo Alberto
Llorente Cortés, Vicenta
author Actis Dato, Virginia
author_facet Actis Dato, Virginia
Benitez Amaro, Aleyda
Garcia, Eduardo
Claudi, Lene
LaChica Lhoëst, Maria Teresa
Iborra, Antoni
Escola Gil, Joan Carles
Guerra, Jose Maria
Samouillan, Valerie
Enrich, Carlos
Chiabrando, Gustavo Alberto
Llorente Cortés, Vicenta
author_role author
author2 Benitez Amaro, Aleyda
Garcia, Eduardo
Claudi, Lene
LaChica Lhoëst, Maria Teresa
Iborra, Antoni
Escola Gil, Joan Carles
Guerra, Jose Maria
Samouillan, Valerie
Enrich, Carlos
Chiabrando, Gustavo Alberto
Llorente Cortés, Vicenta
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHOLESTERYL ESTERS
HEART
HIGH-FAT DIET
INSULIN
LIPID DROPLETS
LIPOPROTEIN
LRP1
topic CHOLESTERYL ESTERS
HEART
HIGH-FAT DIET
INSULIN
LIPID DROPLETS
LIPOPROTEIN
LRP1
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups. Findings: HFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum.
Fil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Benitez Amaro, Aleyda. Consejo Superior de Investigaciones Científicas; España
Fil: Garcia, Eduardo. Consejo Superior de Investigaciones Científicas; España
Fil: Claudi, Lene. Consejo Superior de Investigaciones Científicas; España
Fil: LaChica Lhoëst, Maria Teresa. Consejo Superior de Investigaciones Científicas; España
Fil: Iborra, Antoni. Universitat Autònoma de Barcelona; España
Fil: Escola Gil, Joan Carles. Consejo Superior de Investigaciones Científicas; España
Fil: Guerra, Jose Maria. Universitat Autònoma de Barcelona; España. Instituto de Salud Carlos III; España
Fil: Samouillan, Valerie. Université Paul Sabatier; Francia
Fil: Enrich, Carlos. INSTITUTO DE INVESTIGACIONES BIOMEDICAS AUGUST PI I SUNYER (IDIBAPS); . Universidad de Barcelona; España
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Llorente Cortés, Vicenta. Consejo Superior de Investigaciones Científicas; España
description Background: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups. Findings: HFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum.
publishDate 2022
dc.date.none.fl_str_mv 2022-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/216879
Actis Dato, Virginia; Benitez Amaro, Aleyda; Garcia, Eduardo; Claudi, Lene; LaChica Lhoëst, Maria Teresa; et al.; Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response; Elsevier France-Editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 152; 6-2022; 1-14
0753-3322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216879
identifier_str_mv Actis Dato, Virginia; Benitez Amaro, Aleyda; Garcia, Eduardo; Claudi, Lene; LaChica Lhoëst, Maria Teresa; et al.; Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response; Elsevier France-Editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 152; 6-2022; 1-14
0753-3322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2022.113270
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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