Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity

Background and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPAR alpha agonists on glucose metabolism and the adverse effects associated with selective PPAR gamma activators have stimulated the...

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Autores: Marques, Patrice, Villarroel-Vicente, Carlos, Collado, Aida, Garcia, Ainhoa, Vila, Laura, Duplan, Isabelle, Hennuyer, Nathalie, Garibotto, Francisco, Enriz, Ricardo D, Dacquet, Catherine, Staels, Bart, Piqueras, Laura, Cortes, Diego, Sanz, Maria-Jesus, Cabedo, Nuria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p17115
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/17115
Access Level:acceso abierto
Palabra clave:Prenylated benzopyran
PPAR
Molecular modeling
Metabolic disorders
Anti-inflammatory effects
ob/ob mice
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spelling Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activityMarques, PatriceVillarroel-Vicente, CarlosCollado, AidaGarcia, AinhoaVila, LauraDuplan, IsabelleHennuyer, NathalieGaribotto, FranciscoEnriz, Ricardo DDacquet, CatherineStaels, BartPiqueras, LauraCortes, DiegoSanz, Maria-JesusCabedo, NuriaPrenylated benzopyranPPARMolecular modelingMetabolic disordersAnti-inflammatory effectsob/ob miceBackground and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPAR alpha agonists on glucose metabolism and the adverse effects associated with selective PPAR gamma activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements. Experimental approach: BP-2 was used in transactivation assays to evaluate its agonism to PPAR alpha, PPAR beta/delta and PPAR gamma. A parallel-plate flow chamber was employed to investigate its effect on TNF alpha-induced leukocyteendothelium interactions. Flow cytometry and immunofluorescence were used to determine its effects on the expression of endothelial cell adhesion molecules (CAMs) and chemokines and p38-MAPK/NF-kappa B activation. PPARs/RXR alpha interactions were determined using a gene silencing approach. Analysis of its impact on metabolic abnormalities and inflammation was performed in ob/ob mice. Key results: BP-2 displayed strong PPAR alpha activity, with moderate and weak activity against PPAR beta/delta and PPAR gamma, respectively. In vitro, BP-2 reduced TNF alpha-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPAR beta/delta-RXR alpha interactions and decreased p38-MAPK/NF-kappa B activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed Tlymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206.ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/17115PHARMACOLOGICAL RESEARCHISSN: 10436618ISSNe: 10961186reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p171152026-06-07T16:35:31Z
dc.title.none.fl_str_mv Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
title Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
spellingShingle Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
Marques, Patrice
Prenylated benzopyran
PPAR
Molecular modeling
Metabolic disorders
Anti-inflammatory effects
ob/ob mice
title_short Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
title_full Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
title_fullStr Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
title_full_unstemmed Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
title_sort Anti-inflammatory effects and improved metabolic derangements in <i>ob</i>/<i>ob</i> mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
dc.creator.none.fl_str_mv Marques, Patrice
Villarroel-Vicente, Carlos
Collado, Aida
Garcia, Ainhoa
Vila, Laura
Duplan, Isabelle
Hennuyer, Nathalie
Garibotto, Francisco
Enriz, Ricardo D
Dacquet, Catherine
Staels, Bart
Piqueras, Laura
Cortes, Diego
Sanz, Maria-Jesus
Cabedo, Nuria
author Marques, Patrice
author_facet Marques, Patrice
Villarroel-Vicente, Carlos
Collado, Aida
Garcia, Ainhoa
Vila, Laura
Duplan, Isabelle
Hennuyer, Nathalie
Garibotto, Francisco
Enriz, Ricardo D
Dacquet, Catherine
Staels, Bart
Piqueras, Laura
Cortes, Diego
Sanz, Maria-Jesus
Cabedo, Nuria
author_role author
author2 Villarroel-Vicente, Carlos
Collado, Aida
Garcia, Ainhoa
Vila, Laura
Duplan, Isabelle
Hennuyer, Nathalie
Garibotto, Francisco
Enriz, Ricardo D
Dacquet, Catherine
Staels, Bart
Piqueras, Laura
Cortes, Diego
Sanz, Maria-Jesus
Cabedo, Nuria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prenylated benzopyran
PPAR
Molecular modeling
Metabolic disorders
Anti-inflammatory effects
ob/ob mice
topic Prenylated benzopyran
PPAR
Molecular modeling
Metabolic disorders
Anti-inflammatory effects
ob/ob mice
description Background and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPAR alpha agonists on glucose metabolism and the adverse effects associated with selective PPAR gamma activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements. Experimental approach: BP-2 was used in transactivation assays to evaluate its agonism to PPAR alpha, PPAR beta/delta and PPAR gamma. A parallel-plate flow chamber was employed to investigate its effect on TNF alpha-induced leukocyteendothelium interactions. Flow cytometry and immunofluorescence were used to determine its effects on the expression of endothelial cell adhesion molecules (CAMs) and chemokines and p38-MAPK/NF-kappa B activation. PPARs/RXR alpha interactions were determined using a gene silencing approach. Analysis of its impact on metabolic abnormalities and inflammation was performed in ob/ob mice. Key results: BP-2 displayed strong PPAR alpha activity, with moderate and weak activity against PPAR beta/delta and PPAR gamma, respectively. In vitro, BP-2 reduced TNF alpha-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPAR beta/delta-RXR alpha interactions and decreased p38-MAPK/NF-kappa B activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed Tlymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/17115
url https://incliva.portalinvestigacion.com/publicaciones/17115
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
publisher.none.fl_str_mv ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
dc.source.none.fl_str_mv PHARMACOLOGICAL RESEARCH
ISSN: 10436618
ISSNe: 10961186
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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