Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response

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 re...

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Authors: 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
Format: article
Status:Published version
Publication Date:2022
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/216879
Online Access:http://hdl.handle.net/11336/216879
Access Level:Open access
Keyword:CHOLESTERYL ESTERS
HEART
HIGH-FAT DIET
INSULIN
LIPID DROPLETS
LIPOPROTEIN
LRP1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
id AR_e9b3e694d49e09ed3b92d89a2a6cf2a7
oai_identifier_str oai:ri.conicet.gov.ar:11336/216879
network_acronym_str AR
network_name_str Argentina
repository_id_str
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
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic CHOLESTERYL ESTERS
HEART
HIGH-FAT DIET
INSULIN
LIPID DROPLETS
LIPOPROTEIN
LRP1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799194640975396864
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 Técnicas2024-05-08T13:33:21Zoai: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:34982024-05-08 13:33:21.978CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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