Leptin signaling in Kiss1 neurons arises after pubertal development

Autores
Cravo, Roberta M.; Frazao, Renata; Perello, Mario; Osborne-Lawrence, Sherri; Williams, Kevin W; Zigman, Jeffery M.; Vianna, Claudia; Elias, Carol F.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
 The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing neurons of the arcuate nucleus to exert its effects. Using conditional knockout mice, we have previously demonstrated that deletion of leptin receptors (LepR) from kisspeptin cells cause no puberty or fertility deficits. However, developmental adaptations and system redundancies may have obscured the physiologic relevance of direct leptin signaling in kisspeptin neurons. To overcome these putative effects, we re-expressed endogenous LepR selectively in kisspeptin cells of mice otherwise null for LepR, using the Cre-loxP system. Kiss1-Cre LepR null mice showed no pubertal development and no improvement of the metabolic phenotype, remaining obese, diabetic and infertile. These mice displayed decreased numbers of neurons expressing Kiss1 gene, similar to prepubertal control mice, and an unexpected lack of re-expression of functional LepR. To further assess the temporal coexpression of Kiss1 and Lepr genes, we generated mice with the human renilla green fluorescent protein (hrGFP) driven by Kiss1 regulatory elements and crossed them with mice that express Cre recombinase from the Lepr locus and the R26-tdTomato reporter gene. No coexpression of Kiss1 and LepR was observed in prepubertal mice. Our findings unequivocally demonstrate that kisspeptin neurons are not the direct target of leptin in the onset of puberty. Leptin signaling in kisspeptin neurons arises only after completion of sexual maturation.
Fil: Cravo, Roberta M..
Fil: Frazao, Renata.
Fil: Perello, Mario. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Cs.fisiologicas. Laboratorio de Neurofisiologia;
Fil: Osborne-Lawrence, Sherri.
Fil: Williams, Kevin W.
Fil: Zigman, Jeffery M..
Fil: Vianna, Claudia.
Fil: Elias, Carol F..
Materia
Hipotalamo
neuropeptidos
leptina
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:11336/580

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network_name_str CONICET Digital (CONICET)
spelling Leptin signaling in Kiss1 neurons arises after pubertal developmentCravo, Roberta M.Frazao, RenataPerello, MarioOsborne-Lawrence, SherriWilliams, Kevin WZigman, Jeffery M.Vianna, ClaudiaElias, Carol F.Hipotalamoneuropeptidosleptinahttps://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1 The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing neurons of the arcuate nucleus to exert its effects. Using conditional knockout mice, we have previously demonstrated that deletion of leptin receptors (LepR) from kisspeptin cells cause no puberty or fertility deficits. However, developmental adaptations and system redundancies may have obscured the physiologic relevance of direct leptin signaling in kisspeptin neurons. To overcome these putative effects, we re-expressed endogenous LepR selectively in kisspeptin cells of mice otherwise null for LepR, using the Cre-loxP system. Kiss1-Cre LepR null mice showed no pubertal development and no improvement of the metabolic phenotype, remaining obese, diabetic and infertile. These mice displayed decreased numbers of neurons expressing Kiss1 gene, similar to prepubertal control mice, and an unexpected lack of re-expression of functional LepR. To further assess the temporal coexpression of Kiss1 and Lepr genes, we generated mice with the human renilla green fluorescent protein (hrGFP) driven by Kiss1 regulatory elements and crossed them with mice that express Cre recombinase from the Lepr locus and the R26-tdTomato reporter gene. No coexpression of Kiss1 and LepR was observed in prepubertal mice. Our findings unequivocally demonstrate that kisspeptin neurons are not the direct target of leptin in the onset of puberty. Leptin signaling in kisspeptin neurons arises only after completion of sexual maturation.Fil: Cravo, Roberta M..Fil: Frazao, Renata.Fil: Perello, Mario. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Cs.fisiologicas. Laboratorio de Neurofisiologia;Fil: Osborne-Lawrence, Sherri.Fil: Williams, Kevin W.Fil: Zigman, Jeffery M..Fil: Vianna, Claudia.Fil: Elias, Carol F..Public Library Science2013-03-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/580Cravo, Roberta M.; Frazao, Renata; Perello, Mario; Osborne-Lawrence, Sherri; Williams, Kevin W; Zigman, Jeffery M.; Vianna, Claudia; Elias, Carol F.; Leptin signaling in Kiss1 neurons arises after pubertal development; Public Library Science; Plos One; 7-3-2013; 58698-58699;1932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0058698info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:38Zoai:ri.conicet.gov.ar:11336/580instacron: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 09:49:39.114CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Leptin signaling in Kiss1 neurons arises after pubertal development
title Leptin signaling in Kiss1 neurons arises after pubertal development
spellingShingle Leptin signaling in Kiss1 neurons arises after pubertal development
Cravo, Roberta M.
Hipotalamo
neuropeptidos
leptina
title_short Leptin signaling in Kiss1 neurons arises after pubertal development
title_full Leptin signaling in Kiss1 neurons arises after pubertal development
title_fullStr Leptin signaling in Kiss1 neurons arises after pubertal development
title_full_unstemmed Leptin signaling in Kiss1 neurons arises after pubertal development
title_sort Leptin signaling in Kiss1 neurons arises after pubertal development
dc.creator.none.fl_str_mv Cravo, Roberta M.
Frazao, Renata
Perello, Mario
Osborne-Lawrence, Sherri
Williams, Kevin W
Zigman, Jeffery M.
Vianna, Claudia
Elias, Carol F.
author Cravo, Roberta M.
author_facet Cravo, Roberta M.
Frazao, Renata
Perello, Mario
Osborne-Lawrence, Sherri
Williams, Kevin W
Zigman, Jeffery M.
Vianna, Claudia
Elias, Carol F.
author_role author
author2 Frazao, Renata
Perello, Mario
Osborne-Lawrence, Sherri
Williams, Kevin W
Zigman, Jeffery M.
Vianna, Claudia
Elias, Carol F.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hipotalamo
neuropeptidos
leptina
topic Hipotalamo
neuropeptidos
leptina
purl_subject.fl_str_mv https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
dc.description.none.fl_txt_mv  The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing neurons of the arcuate nucleus to exert its effects. Using conditional knockout mice, we have previously demonstrated that deletion of leptin receptors (LepR) from kisspeptin cells cause no puberty or fertility deficits. However, developmental adaptations and system redundancies may have obscured the physiologic relevance of direct leptin signaling in kisspeptin neurons. To overcome these putative effects, we re-expressed endogenous LepR selectively in kisspeptin cells of mice otherwise null for LepR, using the Cre-loxP system. Kiss1-Cre LepR null mice showed no pubertal development and no improvement of the metabolic phenotype, remaining obese, diabetic and infertile. These mice displayed decreased numbers of neurons expressing Kiss1 gene, similar to prepubertal control mice, and an unexpected lack of re-expression of functional LepR. To further assess the temporal coexpression of Kiss1 and Lepr genes, we generated mice with the human renilla green fluorescent protein (hrGFP) driven by Kiss1 regulatory elements and crossed them with mice that express Cre recombinase from the Lepr locus and the R26-tdTomato reporter gene. No coexpression of Kiss1 and LepR was observed in prepubertal mice. Our findings unequivocally demonstrate that kisspeptin neurons are not the direct target of leptin in the onset of puberty. Leptin signaling in kisspeptin neurons arises only after completion of sexual maturation.
Fil: Cravo, Roberta M..
Fil: Frazao, Renata.
Fil: Perello, Mario. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Cs.fisiologicas. Laboratorio de Neurofisiologia;
Fil: Osborne-Lawrence, Sherri.
Fil: Williams, Kevin W.
Fil: Zigman, Jeffery M..
Fil: Vianna, Claudia.
Fil: Elias, Carol F..
description  The adipocyte-derived hormone leptin is required for normal pubertal maturation in mice and humans and, therefore, leptin has been recognized as a crucial metabolic cue linking energy stores and the onset of puberty. Several lines of evidence have suggested that leptin acts via kisspeptin expressing neurons of the arcuate nucleus to exert its effects. Using conditional knockout mice, we have previously demonstrated that deletion of leptin receptors (LepR) from kisspeptin cells cause no puberty or fertility deficits. However, developmental adaptations and system redundancies may have obscured the physiologic relevance of direct leptin signaling in kisspeptin neurons. To overcome these putative effects, we re-expressed endogenous LepR selectively in kisspeptin cells of mice otherwise null for LepR, using the Cre-loxP system. Kiss1-Cre LepR null mice showed no pubertal development and no improvement of the metabolic phenotype, remaining obese, diabetic and infertile. These mice displayed decreased numbers of neurons expressing Kiss1 gene, similar to prepubertal control mice, and an unexpected lack of re-expression of functional LepR. To further assess the temporal coexpression of Kiss1 and Lepr genes, we generated mice with the human renilla green fluorescent protein (hrGFP) driven by Kiss1 regulatory elements and crossed them with mice that express Cre recombinase from the Lepr locus and the R26-tdTomato reporter gene. No coexpression of Kiss1 and LepR was observed in prepubertal mice. Our findings unequivocally demonstrate that kisspeptin neurons are not the direct target of leptin in the onset of puberty. Leptin signaling in kisspeptin neurons arises only after completion of sexual maturation.
publishDate 2013
dc.date.none.fl_str_mv 2013-03-07
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/11336/580
Cravo, Roberta M.; Frazao, Renata; Perello, Mario; Osborne-Lawrence, Sherri; Williams, Kevin W; Zigman, Jeffery M.; Vianna, Claudia; Elias, Carol F.; Leptin signaling in Kiss1 neurons arises after pubertal development; Public Library Science; Plos One; 7-3-2013; 58698-58699;
1932-6203
url http://hdl.handle.net/11336/580
identifier_str_mv Cravo, Roberta M.; Frazao, Renata; Perello, Mario; Osborne-Lawrence, Sherri; Williams, Kevin W; Zigman, Jeffery M.; Vianna, Claudia; Elias, Carol F.; Leptin signaling in Kiss1 neurons arises after pubertal development; Public Library Science; Plos One; 7-3-2013; 58698-58699;
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0058698
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 Public Library Science
publisher.none.fl_str_mv Public Library Science
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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