Insulin enhances leptin expression in human trophoblastic cells

Autores
Pérez Pérez, Antonio; Maymo, Julieta Lorena; Gambino, Yésica Paola; Guadix, Pilar; Dueñas, José L.; Varone, Cecilia Laura; Sánchez Margalet, Víctor
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Leptin, one of the adipokines that controls energy metabolism via the central nervous system, also has pleiotropic peripheral effects, acting as a proinflammatory cytokine. Leptin is also produced by trophoblastic cells in the placenta, where leptin seems to function as a trophic autocrine hormone. Leptin expression is regulated by various tissue-specific factors, such as insulin, in the adipocyte. However, the complete regulation of leptin production in the placenta is still poorly understood. That is why we investigated the regulation of leptin expression by insulin in JEG-3 trophoblastic cells and human placental explants from normal pregnancies. Western blot analysis and quantitative real time RT-PCR was performed to determine the leptin expression level after treatment of cells or trophoblast explants with different concentrations of insulin (0.1-100 nM). Leptin promoter activity was evaluated by transient transfection with a plasmid construct containing different promoter regions and the reporter luciferase gene. We found a stimulatory, dosedependent effect of insulin on endogenous leptin expression in human placental explants. Maximal effect was achieved at 10 nM insulin, and this effect can be totally prevented both by blocking phosphatidylinositol 3 kinase (PI3K) pathways and mitogen-activated protein kinase (MAPK). Moreover, insulin treatment significantly enhanced leptin promoter activity up to 40% in JEG-3 trophoblastic cells. Deletion analysis demonstrated that a minimal promoter region between -1951 and -1546 bp is necessary to achieve insulin effects. In conclusion, we provide evidence suggesting that insulin induces leptin expression in trophoblastic cells, enhancing the activity of leptin promoter region between -1951 and -1546 bp, via both PI3Kand MAPK-signaling pathways.
Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
Fil: Maymo, Julieta Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Gambino, Yésica Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Guadix, Pilar. Virgen Macarena University Hospital; Estados Unidos
Fil: Dueñas, José L.. Virgen Macarena University Hospital; Estados Unidos
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Sánchez Margalet, Víctor. Universidad de Sevilla; España
Materia
HORMONE ACTION
LEPTIN/LEPTIN RECEPTOR
PLACENTA
SIGNAL TRANSDUCTION
TROPHOBLAST CELLS
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:11336/84440

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Insulin enhances leptin expression in human trophoblastic cellsPérez Pérez, AntonioMaymo, Julieta LorenaGambino, Yésica PaolaGuadix, PilarDueñas, José L.Varone, Cecilia LauraSánchez Margalet, VíctorHORMONE ACTIONLEPTIN/LEPTIN RECEPTORPLACENTASIGNAL TRANSDUCTIONTROPHOBLAST CELLShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Leptin, one of the adipokines that controls energy metabolism via the central nervous system, also has pleiotropic peripheral effects, acting as a proinflammatory cytokine. Leptin is also produced by trophoblastic cells in the placenta, where leptin seems to function as a trophic autocrine hormone. Leptin expression is regulated by various tissue-specific factors, such as insulin, in the adipocyte. However, the complete regulation of leptin production in the placenta is still poorly understood. That is why we investigated the regulation of leptin expression by insulin in JEG-3 trophoblastic cells and human placental explants from normal pregnancies. Western blot analysis and quantitative real time RT-PCR was performed to determine the leptin expression level after treatment of cells or trophoblast explants with different concentrations of insulin (0.1-100 nM). Leptin promoter activity was evaluated by transient transfection with a plasmid construct containing different promoter regions and the reporter luciferase gene. We found a stimulatory, dosedependent effect of insulin on endogenous leptin expression in human placental explants. Maximal effect was achieved at 10 nM insulin, and this effect can be totally prevented both by blocking phosphatidylinositol 3 kinase (PI3K) pathways and mitogen-activated protein kinase (MAPK). Moreover, insulin treatment significantly enhanced leptin promoter activity up to 40% in JEG-3 trophoblastic cells. Deletion analysis demonstrated that a minimal promoter region between -1951 and -1546 bp is necessary to achieve insulin effects. In conclusion, we provide evidence suggesting that insulin induces leptin expression in trophoblastic cells, enhancing the activity of leptin promoter region between -1951 and -1546 bp, via both PI3Kand MAPK-signaling pathways.Fil: Pérez Pérez, Antonio. Universidad de Sevilla; EspañaFil: Maymo, Julieta Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Gambino, Yésica Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Guadix, Pilar. Virgen Macarena University Hospital; Estados UnidosFil: Dueñas, José L.. Virgen Macarena University Hospital; Estados UnidosFil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Sánchez Margalet, Víctor. Universidad de Sevilla; EspañaOxford University Press2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/84440Pérez Pérez, Antonio; Maymo, Julieta Lorena; Gambino, Yésica Paola; Guadix, Pilar; Dueñas, José L.; et al.; Insulin enhances leptin expression in human trophoblastic cells; Oxford University Press; Biology of Reproduction; 89; 1; 6-2013; 20-300006-3363CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1095/biolreprod.113.109348info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biolreprod/article/89/1/20,%201-8/2514210info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:47:01Zoai:ri.conicet.gov.ar:11336/84440instacron: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:34982025-10-15 14:47:01.989CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insulin enhances leptin expression in human trophoblastic cells
title Insulin enhances leptin expression in human trophoblastic cells
spellingShingle Insulin enhances leptin expression in human trophoblastic cells
Pérez Pérez, Antonio
HORMONE ACTION
LEPTIN/LEPTIN RECEPTOR
PLACENTA
SIGNAL TRANSDUCTION
TROPHOBLAST CELLS
title_short Insulin enhances leptin expression in human trophoblastic cells
title_full Insulin enhances leptin expression in human trophoblastic cells
title_fullStr Insulin enhances leptin expression in human trophoblastic cells
title_full_unstemmed Insulin enhances leptin expression in human trophoblastic cells
title_sort Insulin enhances leptin expression in human trophoblastic cells
dc.creator.none.fl_str_mv Pérez Pérez, Antonio
Maymo, Julieta Lorena
Gambino, Yésica Paola
Guadix, Pilar
Dueñas, José L.
Varone, Cecilia Laura
Sánchez Margalet, Víctor
author Pérez Pérez, Antonio
author_facet Pérez Pérez, Antonio
Maymo, Julieta Lorena
Gambino, Yésica Paola
Guadix, Pilar
Dueñas, José L.
Varone, Cecilia Laura
Sánchez Margalet, Víctor
author_role author
author2 Maymo, Julieta Lorena
Gambino, Yésica Paola
Guadix, Pilar
Dueñas, José L.
Varone, Cecilia Laura
Sánchez Margalet, Víctor
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HORMONE ACTION
LEPTIN/LEPTIN RECEPTOR
PLACENTA
SIGNAL TRANSDUCTION
TROPHOBLAST CELLS
topic HORMONE ACTION
LEPTIN/LEPTIN RECEPTOR
PLACENTA
SIGNAL TRANSDUCTION
TROPHOBLAST CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Leptin, one of the adipokines that controls energy metabolism via the central nervous system, also has pleiotropic peripheral effects, acting as a proinflammatory cytokine. Leptin is also produced by trophoblastic cells in the placenta, where leptin seems to function as a trophic autocrine hormone. Leptin expression is regulated by various tissue-specific factors, such as insulin, in the adipocyte. However, the complete regulation of leptin production in the placenta is still poorly understood. That is why we investigated the regulation of leptin expression by insulin in JEG-3 trophoblastic cells and human placental explants from normal pregnancies. Western blot analysis and quantitative real time RT-PCR was performed to determine the leptin expression level after treatment of cells or trophoblast explants with different concentrations of insulin (0.1-100 nM). Leptin promoter activity was evaluated by transient transfection with a plasmid construct containing different promoter regions and the reporter luciferase gene. We found a stimulatory, dosedependent effect of insulin on endogenous leptin expression in human placental explants. Maximal effect was achieved at 10 nM insulin, and this effect can be totally prevented both by blocking phosphatidylinositol 3 kinase (PI3K) pathways and mitogen-activated protein kinase (MAPK). Moreover, insulin treatment significantly enhanced leptin promoter activity up to 40% in JEG-3 trophoblastic cells. Deletion analysis demonstrated that a minimal promoter region between -1951 and -1546 bp is necessary to achieve insulin effects. In conclusion, we provide evidence suggesting that insulin induces leptin expression in trophoblastic cells, enhancing the activity of leptin promoter region between -1951 and -1546 bp, via both PI3Kand MAPK-signaling pathways.
Fil: Pérez Pérez, Antonio. Universidad de Sevilla; España
Fil: Maymo, Julieta Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Gambino, Yésica Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Guadix, Pilar. Virgen Macarena University Hospital; Estados Unidos
Fil: Dueñas, José L.. Virgen Macarena University Hospital; Estados Unidos
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Sánchez Margalet, Víctor. Universidad de Sevilla; España
description Leptin, one of the adipokines that controls energy metabolism via the central nervous system, also has pleiotropic peripheral effects, acting as a proinflammatory cytokine. Leptin is also produced by trophoblastic cells in the placenta, where leptin seems to function as a trophic autocrine hormone. Leptin expression is regulated by various tissue-specific factors, such as insulin, in the adipocyte. However, the complete regulation of leptin production in the placenta is still poorly understood. That is why we investigated the regulation of leptin expression by insulin in JEG-3 trophoblastic cells and human placental explants from normal pregnancies. Western blot analysis and quantitative real time RT-PCR was performed to determine the leptin expression level after treatment of cells or trophoblast explants with different concentrations of insulin (0.1-100 nM). Leptin promoter activity was evaluated by transient transfection with a plasmid construct containing different promoter regions and the reporter luciferase gene. We found a stimulatory, dosedependent effect of insulin on endogenous leptin expression in human placental explants. Maximal effect was achieved at 10 nM insulin, and this effect can be totally prevented both by blocking phosphatidylinositol 3 kinase (PI3K) pathways and mitogen-activated protein kinase (MAPK). Moreover, insulin treatment significantly enhanced leptin promoter activity up to 40% in JEG-3 trophoblastic cells. Deletion analysis demonstrated that a minimal promoter region between -1951 and -1546 bp is necessary to achieve insulin effects. In conclusion, we provide evidence suggesting that insulin induces leptin expression in trophoblastic cells, enhancing the activity of leptin promoter region between -1951 and -1546 bp, via both PI3Kand MAPK-signaling pathways.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/84440
Pérez Pérez, Antonio; Maymo, Julieta Lorena; Gambino, Yésica Paola; Guadix, Pilar; Dueñas, José L.; et al.; Insulin enhances leptin expression in human trophoblastic cells; Oxford University Press; Biology of Reproduction; 89; 1; 6-2013; 20-30
0006-3363
CONICET Digital
CONICET
url http://hdl.handle.net/11336/84440
identifier_str_mv Pérez Pérez, Antonio; Maymo, Julieta Lorena; Gambino, Yésica Paola; Guadix, Pilar; Dueñas, José L.; et al.; Insulin enhances leptin expression in human trophoblastic cells; Oxford University Press; Biology of Reproduction; 89; 1; 6-2013; 20-30
0006-3363
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1095/biolreprod.113.109348
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biolreprod/article/89/1/20,%201-8/2514210
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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