Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity
- Autores
- Marques, Patrice; Villarroel Vicente, Carlos; Collado, Aida; García, Ainhoa; Vila, Laura; Duplan, Isabelle; Hennuyer, Nathalie; Garibotto, Francisco Matías; Enriz, Ricardo Daniel; Dacquet, Catherine; Staels, Bart; Piqueras, Laura; Cortes, Diego; Sanz, María Jesús; Cabedo, Nuria
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ 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 PPARα, PPARβ/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium 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-κB activation. PPARs/RXRα 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 PPARα activity, with moderate and weak activity against PPARβ/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARβ/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. Conclusion and implications: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications.
Fil: Marques, Patrice. Universidad de Valencia; España
Fil: Villarroel Vicente, Carlos. Universidad de Valencia; España
Fil: Collado, Aida. Universidad de Valencia; España
Fil: García, Ainhoa. Universidad de Valencia; España
Fil: Vila, Laura. Hospital Clinico Universitario de Valencia; España
Fil: Duplan, Isabelle. University Of Lille.; Francia
Fil: Hennuyer, Nathalie. University Of Lille.; Francia
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Dacquet, Catherine. No especifíca;
Fil: Staels, Bart. University Of Lille.; Francia
Fil: Piqueras, Laura. Universidad de Valencia; España
Fil: Cortes, Diego. Universidad de Valencia; España
Fil: Sanz, María Jesús. Universidad de Valencia; España
Fil: Cabedo, Nuria. Universidad de Valencia; España - Materia
-
ANTI-INFLAMMATORY EFFECTS
GW501516 OR ENDUROBOL (PUBCHEM CID: 9803963)
METABOLIC DISORDERS
MOLECULAR MODELING
OB/OB MICE
PPAR
PRENYLATED BENZOPYRAN
ROSIGLITAZONE (PUBCHEM CID: 77999)
WY-14,643 OR PIRINIXIC ACID (PUBCHEM CID: 5694) - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/219488
Ver los metadatos del registro completo
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Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activityMarques, PatriceVillarroel Vicente, CarlosCollado, AidaGarcía, AinhoaVila, LauraDuplan, IsabelleHennuyer, NathalieGaribotto, Francisco MatíasEnriz, Ricardo DanielDacquet, CatherineStaels, BartPiqueras, LauraCortes, DiegoSanz, María JesúsCabedo, NuriaANTI-INFLAMMATORY EFFECTSGW501516 OR ENDUROBOL (PUBCHEM CID: 9803963)METABOLIC DISORDERSMOLECULAR MODELINGOB/OB MICEPPARPRENYLATED BENZOPYRANROSIGLITAZONE (PUBCHEM CID: 77999)WY-14,643 OR PIRINIXIC ACID (PUBCHEM CID: 5694)https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Background and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ 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 PPARα, PPARβ/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium 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-κB activation. PPARs/RXRα 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 PPARα activity, with moderate and weak activity against PPARβ/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARβ/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. Conclusion and implications: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications.Fil: Marques, Patrice. Universidad de Valencia; EspañaFil: Villarroel Vicente, Carlos. Universidad de Valencia; EspañaFil: Collado, Aida. Universidad de Valencia; EspañaFil: García, Ainhoa. Universidad de Valencia; EspañaFil: Vila, Laura. Hospital Clinico Universitario de Valencia; EspañaFil: Duplan, Isabelle. University Of Lille.; FranciaFil: Hennuyer, Nathalie. University Of Lille.; FranciaFil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Dacquet, Catherine. No especifíca;Fil: Staels, Bart. University Of Lille.; FranciaFil: Piqueras, Laura. Universidad de Valencia; EspañaFil: Cortes, Diego. Universidad de Valencia; EspañaFil: Sanz, María Jesús. Universidad de Valencia; EspañaFil: Cabedo, Nuria. Universidad de Valencia; EspañaAcademic Press Ltd - Elsevier Science Ltd2023-01info: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/11336/219488Marques, Patrice; Villarroel Vicente, Carlos; Collado, Aida; García, Ainhoa; Vila, Laura; et al.; Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 187; 1-2023; 1-141043-6618CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.phrs.2022.106638info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:56Zoai:ri.conicet.gov.ar:11336/219488instacron: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 09:56:56.325CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| title |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| spellingShingle |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity Marques, Patrice ANTI-INFLAMMATORY EFFECTS GW501516 OR ENDUROBOL (PUBCHEM CID: 9803963) METABOLIC DISORDERS MOLECULAR MODELING OB/OB MICE PPAR PRENYLATED BENZOPYRAN ROSIGLITAZONE (PUBCHEM CID: 77999) WY-14,643 OR PIRINIXIC ACID (PUBCHEM CID: 5694) |
| title_short |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| title_full |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| title_fullStr |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| title_full_unstemmed |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| title_sort |
Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity |
| dc.creator.none.fl_str_mv |
Marques, Patrice Villarroel Vicente, Carlos Collado, Aida García, Ainhoa Vila, Laura Duplan, Isabelle Hennuyer, Nathalie Garibotto, Francisco Matías Enriz, Ricardo Daniel Dacquet, Catherine Staels, Bart Piqueras, Laura Cortes, Diego Sanz, María Jesús Cabedo, Nuria |
| author |
Marques, Patrice |
| author_facet |
Marques, Patrice Villarroel Vicente, Carlos Collado, Aida García, Ainhoa Vila, Laura Duplan, Isabelle Hennuyer, Nathalie Garibotto, Francisco Matías Enriz, Ricardo Daniel Dacquet, Catherine Staels, Bart Piqueras, Laura Cortes, Diego Sanz, María Jesús Cabedo, Nuria |
| author_role |
author |
| author2 |
Villarroel Vicente, Carlos Collado, Aida García, Ainhoa Vila, Laura Duplan, Isabelle Hennuyer, Nathalie Garibotto, Francisco Matías Enriz, Ricardo Daniel Dacquet, Catherine Staels, Bart Piqueras, Laura Cortes, Diego Sanz, María Jesús Cabedo, Nuria |
| author2_role |
author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ANTI-INFLAMMATORY EFFECTS GW501516 OR ENDUROBOL (PUBCHEM CID: 9803963) METABOLIC DISORDERS MOLECULAR MODELING OB/OB MICE PPAR PRENYLATED BENZOPYRAN ROSIGLITAZONE (PUBCHEM CID: 77999) WY-14,643 OR PIRINIXIC ACID (PUBCHEM CID: 5694) |
| topic |
ANTI-INFLAMMATORY EFFECTS GW501516 OR ENDUROBOL (PUBCHEM CID: 9803963) METABOLIC DISORDERS MOLECULAR MODELING OB/OB MICE PPAR PRENYLATED BENZOPYRAN ROSIGLITAZONE (PUBCHEM CID: 77999) WY-14,643 OR PIRINIXIC ACID (PUBCHEM CID: 5694) |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
Background and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ 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 PPARα, PPARβ/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium 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-κB activation. PPARs/RXRα 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 PPARα activity, with moderate and weak activity against PPARβ/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARβ/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. Conclusion and implications: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications. Fil: Marques, Patrice. Universidad de Valencia; España Fil: Villarroel Vicente, Carlos. Universidad de Valencia; España Fil: Collado, Aida. Universidad de Valencia; España Fil: García, Ainhoa. Universidad de Valencia; España Fil: Vila, Laura. Hospital Clinico Universitario de Valencia; España Fil: Duplan, Isabelle. University Of Lille.; Francia Fil: Hennuyer, Nathalie. University Of Lille.; Francia Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Dacquet, Catherine. No especifíca; Fil: Staels, Bart. University Of Lille.; Francia Fil: Piqueras, Laura. Universidad de Valencia; España Fil: Cortes, Diego. Universidad de Valencia; España Fil: Sanz, María Jesús. Universidad de Valencia; España Fil: Cabedo, Nuria. Universidad de Valencia; España |
| description |
Background and purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ 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 PPARα, PPARβ/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium 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-κB activation. PPARs/RXRα 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 PPARα activity, with moderate and weak activity against PPARβ/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARβ/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. Conclusion and implications: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-01 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
| status_str |
publishedVersion |
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http://hdl.handle.net/11336/219488 Marques, Patrice; Villarroel Vicente, Carlos; Collado, Aida; García, Ainhoa; Vila, Laura; et al.; Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 187; 1-2023; 1-14 1043-6618 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/219488 |
| identifier_str_mv |
Marques, Patrice; Villarroel Vicente, Carlos; Collado, Aida; García, Ainhoa; Vila, Laura; et al.; Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 187; 1-2023; 1-14 1043-6618 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phrs.2022.106638 |
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openAccess |
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https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
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application/pdf application/pdf application/pdf |
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Academic Press Ltd - Elsevier Science Ltd |
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Academic Press Ltd - Elsevier Science Ltd |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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