Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity

Autores
Pandolfi, Julieta Belen; Ferraro, A.; Lerner, M.; Serrano, J. R.; Dueck, A.; Fainboim, Leonardo; Arruvito, Maria Lourdes
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Obesity is accompanied by chronic inflammation of VAT, which promotes metabolic changes, and purinergic signaling has a key role in a wide range of inflammatory diseases. Therefore, we addressed whether fat inflammation could be differentially modulated by this signaling pathway in the MUO and in individuals who remain MHO. Our results show that the necrotized VAT of both groups released greater levels of ATP compared with lean donors. Interestingly, MUO tissue SVCs showed up-regulation and engagement of the purinergic P2X7R. The extracellular ATP concentration is regulated by an enzymatic process, in which CD39 converts ATP and ADP into AMP, and CD73 converts AMP into adenosine. In VAT, the CD73 ectoenzyme was widely distributed in immune and nonimmune cells, whereas CD39 expression was restricted to immune CD45PAN+ SVCs. Although the MUO group expressed the highest levels of both ectoenzymes, no difference in ATP hydrolysis capacity was found between the groups. As expected, MUO exhibited the highest NLRP3 inflammasome expression and IL-1β production. MUO SVCs also displayed up-regulation of the A2AR, allowing extracellular adenosine to increase IL-1β local secretion. Additionally, we demonstrate that metabolic parameters and BMI are positively correlated with purinergic components in VAT. These findings indicate that purinergic signaling is a novel mechanism involved in the chronic inflammation of VAT underlying the metabolic changes in obesity. Finally, our study reveals a proinflammatory role for adenosine in sustaining IL-1β production in this tissue.
Fil: Pandolfi, Julieta Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Ferraro, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Lerner, M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Serrano, J. R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Dueck, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Fainboim, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Arruvito, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Materia
Atp
Adenosine
Inflammation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18757
Acceder
id CONICETDig_4710217dbe0d32e593548f2540e594d8
oai_identifier_str oai:ri.conicet.gov.ar:11336/18757
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesityPandolfi, Julieta BelenFerraro, A.Lerner, M.Serrano, J. R.Dueck, A.Fainboim, LeonardoArruvito, Maria LourdesAtpAdenosineInflammationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Obesity is accompanied by chronic inflammation of VAT, which promotes metabolic changes, and purinergic signaling has a key role in a wide range of inflammatory diseases. Therefore, we addressed whether fat inflammation could be differentially modulated by this signaling pathway in the MUO and in individuals who remain MHO. Our results show that the necrotized VAT of both groups released greater levels of ATP compared with lean donors. Interestingly, MUO tissue SVCs showed up-regulation and engagement of the purinergic P2X7R. The extracellular ATP concentration is regulated by an enzymatic process, in which CD39 converts ATP and ADP into AMP, and CD73 converts AMP into adenosine. In VAT, the CD73 ectoenzyme was widely distributed in immune and nonimmune cells, whereas CD39 expression was restricted to immune CD45PAN+ SVCs. Although the MUO group expressed the highest levels of both ectoenzymes, no difference in ATP hydrolysis capacity was found between the groups. As expected, MUO exhibited the highest NLRP3 inflammasome expression and IL-1β production. MUO SVCs also displayed up-regulation of the A2AR, allowing extracellular adenosine to increase IL-1β local secretion. Additionally, we demonstrate that metabolic parameters and BMI are positively correlated with purinergic components in VAT. These findings indicate that purinergic signaling is a novel mechanism involved in the chronic inflammation of VAT underlying the metabolic changes in obesity. Finally, our study reveals a proinflammatory role for adenosine in sustaining IL-1β production in this tissue.Fil: Pandolfi, Julieta Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Ferraro, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Lerner, M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Serrano, J. R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Dueck, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Fainboim, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Arruvito, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaSociety for Leukocyte Biology2015-05info: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/11336/18757Pandolfi, Julieta Belen; Ferraro, A.; Lerner, M.; Serrano, J. R.; Dueck, A.; et al.; Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity; Society for Leukocyte Biology; Journal of Leukocyte Biology; 97; 5; 5-2015; 941-9490741-54001938-3673CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1189/jlb.3A1214-626Rinfo:eu-repo/semantics/altIdentifier/url/https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.3A1214-626Rinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:39Zoai:ri.conicet.gov.ar:11336/18757instacron: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:34982025-09-03 09:51:39.528CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
title Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
spellingShingle Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
Pandolfi, Julieta Belen
Atp
Adenosine
Inflammation
title_short Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
title_full Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
title_fullStr Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
title_full_unstemmed Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
title_sort Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity
dc.creator.none.fl_str_mv Pandolfi, Julieta Belen
Ferraro, A.
Lerner, M.
Serrano, J. R.
Dueck, A.
Fainboim, Leonardo
Arruvito, Maria Lourdes
author Pandolfi, Julieta Belen
author_facet Pandolfi, Julieta Belen
Ferraro, A.
Lerner, M.
Serrano, J. R.
Dueck, A.
Fainboim, Leonardo
Arruvito, Maria Lourdes
author_role author
author2 Ferraro, A.
Lerner, M.
Serrano, J. R.
Dueck, A.
Fainboim, Leonardo
Arruvito, Maria Lourdes
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Atp
Adenosine
Inflammation
topic Atp
Adenosine
Inflammation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Obesity is accompanied by chronic inflammation of VAT, which promotes metabolic changes, and purinergic signaling has a key role in a wide range of inflammatory diseases. Therefore, we addressed whether fat inflammation could be differentially modulated by this signaling pathway in the MUO and in individuals who remain MHO. Our results show that the necrotized VAT of both groups released greater levels of ATP compared with lean donors. Interestingly, MUO tissue SVCs showed up-regulation and engagement of the purinergic P2X7R. The extracellular ATP concentration is regulated by an enzymatic process, in which CD39 converts ATP and ADP into AMP, and CD73 converts AMP into adenosine. In VAT, the CD73 ectoenzyme was widely distributed in immune and nonimmune cells, whereas CD39 expression was restricted to immune CD45PAN+ SVCs. Although the MUO group expressed the highest levels of both ectoenzymes, no difference in ATP hydrolysis capacity was found between the groups. As expected, MUO exhibited the highest NLRP3 inflammasome expression and IL-1β production. MUO SVCs also displayed up-regulation of the A2AR, allowing extracellular adenosine to increase IL-1β local secretion. Additionally, we demonstrate that metabolic parameters and BMI are positively correlated with purinergic components in VAT. These findings indicate that purinergic signaling is a novel mechanism involved in the chronic inflammation of VAT underlying the metabolic changes in obesity. Finally, our study reveals a proinflammatory role for adenosine in sustaining IL-1β production in this tissue.
Fil: Pandolfi, Julieta Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Ferraro, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Lerner, M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Serrano, J. R.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Dueck, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Fainboim, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Arruvito, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
description Obesity is accompanied by chronic inflammation of VAT, which promotes metabolic changes, and purinergic signaling has a key role in a wide range of inflammatory diseases. Therefore, we addressed whether fat inflammation could be differentially modulated by this signaling pathway in the MUO and in individuals who remain MHO. Our results show that the necrotized VAT of both groups released greater levels of ATP compared with lean donors. Interestingly, MUO tissue SVCs showed up-regulation and engagement of the purinergic P2X7R. The extracellular ATP concentration is regulated by an enzymatic process, in which CD39 converts ATP and ADP into AMP, and CD73 converts AMP into adenosine. In VAT, the CD73 ectoenzyme was widely distributed in immune and nonimmune cells, whereas CD39 expression was restricted to immune CD45PAN+ SVCs. Although the MUO group expressed the highest levels of both ectoenzymes, no difference in ATP hydrolysis capacity was found between the groups. As expected, MUO exhibited the highest NLRP3 inflammasome expression and IL-1β production. MUO SVCs also displayed up-regulation of the A2AR, allowing extracellular adenosine to increase IL-1β local secretion. Additionally, we demonstrate that metabolic parameters and BMI are positively correlated with purinergic components in VAT. These findings indicate that purinergic signaling is a novel mechanism involved in the chronic inflammation of VAT underlying the metabolic changes in obesity. Finally, our study reveals a proinflammatory role for adenosine in sustaining IL-1β production in this tissue.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
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/11336/18757
Pandolfi, Julieta Belen; Ferraro, A.; Lerner, M.; Serrano, J. R.; Dueck, A.; et al.; Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity; Society for Leukocyte Biology; Journal of Leukocyte Biology; 97; 5; 5-2015; 941-949
0741-5400
1938-3673
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18757
identifier_str_mv Pandolfi, Julieta Belen; Ferraro, A.; Lerner, M.; Serrano, J. R.; Dueck, A.; et al.; Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity; Society for Leukocyte Biology; Journal of Leukocyte Biology; 97; 5; 5-2015; 941-949
0741-5400
1938-3673
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1189/jlb.3A1214-626R
info:eu-repo/semantics/altIdentifier/url/https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.3A1214-626R
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Leukocyte Biology
publisher.none.fl_str_mv Society for Leukocyte Biology
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
_version_ 1842269108429651968
score 13.13397

Publicaciones similares