Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis

Autores
Gong, Lijie; Yao, Fayi; Hockman, Kristin; Heng, Henry H.; Morton, Gregory J.; Takeda, Kiyoshi; Akira, Shizuo; Low, Malcolm J.; Rubinstein, Marcelo; MacKenzie, Robert G.
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Signal transducer and activator of transcription (Stat)-3 signals mediate many of the metabolic effects of the fat cell-derived hormone, leptin. In mice, brain-specific depletion of either the long form of the leptin receptor (Lepr) or Stat3 results in comparable obese phenotypes as does replacement of Lepr with an altered leptin receptor locus that codes for a Lepr unable to interact with Stat3. Among the multiple brain regions containing leptin-sensitive Stat3 sites, cells expressing feeding-related neuropeptides in the arcuate nucleus of the hypothalamus have received much of the focus. To determine the contribution to energy homeostasis of Stat3 expressed in agouti-related protein (Agrp)/neuropeptide Y (Npy) arcuate neurons, Stat3 was deleted specifically from these cells, and several metabolic indices were measured. It was found that deletion of Stat3 from Agrp/Npy neurons resulted in modest weight gain that was accounted for by increased adiposity. Agrp/Stat3-deficient mice also showed hyperleptinemia, and high-fat diet-induced hyperinsulinemia. Stat3 deletion in Agrp/Npy neurons also resulted in altered hypothalamic gene expression indicated by increased Npy mRNA and decreased induction of suppressor of cytokine signaling-3 in response to leptin. Agrp mRNA levels in the fed or fasted state were unaffected. Behaviorally, mice without Stat3 in Agrp/Npy neurons were mildly hyperphagic and hyporesponsive to leptin. We conclude that Stat3 in Agrp/Npy neurons is required for normal energy homeostasis, but Stat3 signaling in other brain areas also contributes to the regulation of energy homeostasis.
Fil: Gong, Lijie. Wayne State University School of Medicine; Estados Unidos
Fil: Yao, Fayi. Wayne State University School of Medicine; Estados Unidos
Fil: Hockman, Kristin. Wayne State University School of Medicine; Estados Unidos
Fil: Heng, Henry H.. Wayne State University School of Medicine; Estados Unidos
Fil: Morton, Gregory J.. University of Washington; Estados Unidos
Fil: Takeda, Kiyoshi. Kyushu University; Japón
Fil: Akira, Shizuo. Osaka University; Japón
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: MacKenzie, Robert G.. Wayne State University School of Medicine; Estados Unidos
Materia
Stat3
Agrp
Npy
Pomc
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:11336/79642
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79642
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasisGong, LijieYao, FayiHockman, KristinHeng, Henry H.Morton, Gregory J.Takeda, KiyoshiAkira, ShizuoLow, Malcolm J.Rubinstein, MarceloMacKenzie, Robert G.Stat3AgrpNpyPomchttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Signal transducer and activator of transcription (Stat)-3 signals mediate many of the metabolic effects of the fat cell-derived hormone, leptin. In mice, brain-specific depletion of either the long form of the leptin receptor (Lepr) or Stat3 results in comparable obese phenotypes as does replacement of Lepr with an altered leptin receptor locus that codes for a Lepr unable to interact with Stat3. Among the multiple brain regions containing leptin-sensitive Stat3 sites, cells expressing feeding-related neuropeptides in the arcuate nucleus of the hypothalamus have received much of the focus. To determine the contribution to energy homeostasis of Stat3 expressed in agouti-related protein (Agrp)/neuropeptide Y (Npy) arcuate neurons, Stat3 was deleted specifically from these cells, and several metabolic indices were measured. It was found that deletion of Stat3 from Agrp/Npy neurons resulted in modest weight gain that was accounted for by increased adiposity. Agrp/Stat3-deficient mice also showed hyperleptinemia, and high-fat diet-induced hyperinsulinemia. Stat3 deletion in Agrp/Npy neurons also resulted in altered hypothalamic gene expression indicated by increased Npy mRNA and decreased induction of suppressor of cytokine signaling-3 in response to leptin. Agrp mRNA levels in the fed or fasted state were unaffected. Behaviorally, mice without Stat3 in Agrp/Npy neurons were mildly hyperphagic and hyporesponsive to leptin. We conclude that Stat3 in Agrp/Npy neurons is required for normal energy homeostasis, but Stat3 signaling in other brain areas also contributes to the regulation of energy homeostasis.Fil: Gong, Lijie. Wayne State University School of Medicine; Estados UnidosFil: Yao, Fayi. Wayne State University School of Medicine; Estados UnidosFil: Hockman, Kristin. Wayne State University School of Medicine; Estados UnidosFil: Heng, Henry H.. Wayne State University School of Medicine; Estados UnidosFil: Morton, Gregory J.. University of Washington; Estados UnidosFil: Takeda, Kiyoshi. Kyushu University; JapónFil: Akira, Shizuo. Osaka University; JapónFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: MacKenzie, Robert G.. Wayne State University School of Medicine; Estados UnidosOxford University Press2008-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79642Gong, Lijie; Yao, Fayi; Hockman, Kristin; Heng, Henry H.; Morton, Gregory J.; et al.; Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis; Oxford University Press; Endocrinology; 149; 7; 7-2008; 3346-33540013-7227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1210/en.2007-0945info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/149/7/3346/2454947info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:26Zoai:ri.conicet.gov.ar:11336/79642instacron: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 09:57:27.14CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
title Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
spellingShingle Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
Gong, Lijie
Stat3
Agrp
Npy
Pomc
title_short Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
title_full Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
title_fullStr Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
title_full_unstemmed Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
title_sort Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis
dc.creator.none.fl_str_mv Gong, Lijie
Yao, Fayi
Hockman, Kristin
Heng, Henry H.
Morton, Gregory J.
Takeda, Kiyoshi
Akira, Shizuo
Low, Malcolm J.
Rubinstein, Marcelo
MacKenzie, Robert G.
author Gong, Lijie
author_facet Gong, Lijie
Yao, Fayi
Hockman, Kristin
Heng, Henry H.
Morton, Gregory J.
Takeda, Kiyoshi
Akira, Shizuo
Low, Malcolm J.
Rubinstein, Marcelo
MacKenzie, Robert G.
author_role author
author2 Yao, Fayi
Hockman, Kristin
Heng, Henry H.
Morton, Gregory J.
Takeda, Kiyoshi
Akira, Shizuo
Low, Malcolm J.
Rubinstein, Marcelo
MacKenzie, Robert G.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Stat3
Agrp
Npy
Pomc
topic Stat3
Agrp
Npy
Pomc
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Signal transducer and activator of transcription (Stat)-3 signals mediate many of the metabolic effects of the fat cell-derived hormone, leptin. In mice, brain-specific depletion of either the long form of the leptin receptor (Lepr) or Stat3 results in comparable obese phenotypes as does replacement of Lepr with an altered leptin receptor locus that codes for a Lepr unable to interact with Stat3. Among the multiple brain regions containing leptin-sensitive Stat3 sites, cells expressing feeding-related neuropeptides in the arcuate nucleus of the hypothalamus have received much of the focus. To determine the contribution to energy homeostasis of Stat3 expressed in agouti-related protein (Agrp)/neuropeptide Y (Npy) arcuate neurons, Stat3 was deleted specifically from these cells, and several metabolic indices were measured. It was found that deletion of Stat3 from Agrp/Npy neurons resulted in modest weight gain that was accounted for by increased adiposity. Agrp/Stat3-deficient mice also showed hyperleptinemia, and high-fat diet-induced hyperinsulinemia. Stat3 deletion in Agrp/Npy neurons also resulted in altered hypothalamic gene expression indicated by increased Npy mRNA and decreased induction of suppressor of cytokine signaling-3 in response to leptin. Agrp mRNA levels in the fed or fasted state were unaffected. Behaviorally, mice without Stat3 in Agrp/Npy neurons were mildly hyperphagic and hyporesponsive to leptin. We conclude that Stat3 in Agrp/Npy neurons is required for normal energy homeostasis, but Stat3 signaling in other brain areas also contributes to the regulation of energy homeostasis.
Fil: Gong, Lijie. Wayne State University School of Medicine; Estados Unidos
Fil: Yao, Fayi. Wayne State University School of Medicine; Estados Unidos
Fil: Hockman, Kristin. Wayne State University School of Medicine; Estados Unidos
Fil: Heng, Henry H.. Wayne State University School of Medicine; Estados Unidos
Fil: Morton, Gregory J.. University of Washington; Estados Unidos
Fil: Takeda, Kiyoshi. Kyushu University; Japón
Fil: Akira, Shizuo. Osaka University; Japón
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: MacKenzie, Robert G.. Wayne State University School of Medicine; Estados Unidos
description Signal transducer and activator of transcription (Stat)-3 signals mediate many of the metabolic effects of the fat cell-derived hormone, leptin. In mice, brain-specific depletion of either the long form of the leptin receptor (Lepr) or Stat3 results in comparable obese phenotypes as does replacement of Lepr with an altered leptin receptor locus that codes for a Lepr unable to interact with Stat3. Among the multiple brain regions containing leptin-sensitive Stat3 sites, cells expressing feeding-related neuropeptides in the arcuate nucleus of the hypothalamus have received much of the focus. To determine the contribution to energy homeostasis of Stat3 expressed in agouti-related protein (Agrp)/neuropeptide Y (Npy) arcuate neurons, Stat3 was deleted specifically from these cells, and several metabolic indices were measured. It was found that deletion of Stat3 from Agrp/Npy neurons resulted in modest weight gain that was accounted for by increased adiposity. Agrp/Stat3-deficient mice also showed hyperleptinemia, and high-fat diet-induced hyperinsulinemia. Stat3 deletion in Agrp/Npy neurons also resulted in altered hypothalamic gene expression indicated by increased Npy mRNA and decreased induction of suppressor of cytokine signaling-3 in response to leptin. Agrp mRNA levels in the fed or fasted state were unaffected. Behaviorally, mice without Stat3 in Agrp/Npy neurons were mildly hyperphagic and hyporesponsive to leptin. We conclude that Stat3 in Agrp/Npy neurons is required for normal energy homeostasis, but Stat3 signaling in other brain areas also contributes to the regulation of energy homeostasis.
publishDate 2008
dc.date.none.fl_str_mv 2008-07
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/11336/79642
Gong, Lijie; Yao, Fayi; Hockman, Kristin; Heng, Henry H.; Morton, Gregory J.; et al.; Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis; Oxford University Press; Endocrinology; 149; 7; 7-2008; 3346-3354
0013-7227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79642
identifier_str_mv Gong, Lijie; Yao, Fayi; Hockman, Kristin; Heng, Henry H.; Morton, Gregory J.; et al.; Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis; Oxford University Press; Endocrinology; 149; 7; 7-2008; 3346-3354
0013-7227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2007-0945
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/149/7/3346/2454947
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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score 13.13397

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