Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus

Autores
Cowley, Michael A.; Smart, James L.; Rubinstein, Marcelo; Cerdán, Marcelo G.; Diano, Sabrina; Horvath, Tamas L.; Cone, Roger D.; Low, Malcolm J.
Año de publicación
2001
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (γ-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus.
Fil: Cowley, Michael A.. Oregon Health Sciences University; Estados Unidos
Fil: Smart, James L.. Oregon Health Sciences 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: Cerdán, Marcelo G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Diano, Sabrina. Yale Medical School; Estados Unidos
Fil: Horvath, Tamas L.. Yale Medical School; Estados Unidos
Fil: Cone, Roger D.. Oregon Health Sciences University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos
Materia
leptina
saciedad
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:11336/71802
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleusCowley, Michael A.Smart, James L.Rubinstein, MarceloCerdán, Marcelo G.Diano, SabrinaHorvath, Tamas L.Cone, Roger D.Low, Malcolm J.leptinasaciedadhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (γ-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus.Fil: Cowley, Michael A.. Oregon Health Sciences University; Estados UnidosFil: Smart, James L.. Oregon Health Sciences 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: Cerdán, Marcelo G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Diano, Sabrina. Yale Medical School; Estados UnidosFil: Horvath, Tamas L.. Yale Medical School; Estados UnidosFil: Cone, Roger D.. Oregon Health Sciences University; Estados UnidosFil: Low, Malcolm J.. Oregon Health Sciences University; Estados UnidosNature Publishing Group2001-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71802Cowley, Michael A.; Smart, James L.; Rubinstein, Marcelo; Cerdán, Marcelo G.; Diano, Sabrina; et al.; Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus; Nature Publishing Group; Nature; 411; 6836; 5-2001; 480-4840028-0836CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/35078085info:eu-repo/semantics/altIdentifier/doi/10.1038/35078085info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:10:53Zoai:ri.conicet.gov.ar:11336/71802instacron: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:34982025-09-10 13:10:54.078CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
spellingShingle Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, Michael A.
leptina
saciedad
title_short Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_full Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_fullStr Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_full_unstemmed Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
title_sort Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
dc.creator.none.fl_str_mv Cowley, Michael A.
Smart, James L.
Rubinstein, Marcelo
Cerdán, Marcelo G.
Diano, Sabrina
Horvath, Tamas L.
Cone, Roger D.
Low, Malcolm J.
author Cowley, Michael A.
author_facet Cowley, Michael A.
Smart, James L.
Rubinstein, Marcelo
Cerdán, Marcelo G.
Diano, Sabrina
Horvath, Tamas L.
Cone, Roger D.
Low, Malcolm J.
author_role author
author2 Smart, James L.
Rubinstein, Marcelo
Cerdán, Marcelo G.
Diano, Sabrina
Horvath, Tamas L.
Cone, Roger D.
Low, Malcolm J.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv leptina
saciedad
topic leptina
saciedad
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (γ-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus.
Fil: Cowley, Michael A.. Oregon Health Sciences University; Estados Unidos
Fil: Smart, James L.. Oregon Health Sciences 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: Cerdán, Marcelo G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Diano, Sabrina. Yale Medical School; Estados Unidos
Fil: Horvath, Tamas L.. Yale Medical School; Estados Unidos
Fil: Cone, Roger D.. Oregon Health Sciences University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos
description The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (γ-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus.
publishDate 2001
dc.date.none.fl_str_mv 2001-05
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/11336/71802
Cowley, Michael A.; Smart, James L.; Rubinstein, Marcelo; Cerdán, Marcelo G.; Diano, Sabrina; et al.; Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus; Nature Publishing Group; Nature; 411; 6836; 5-2001; 480-484
0028-0836
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71802
identifier_str_mv Cowley, Michael A.; Smart, James L.; Rubinstein, Marcelo; Cerdán, Marcelo G.; Diano, Sabrina; et al.; Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus; Nature Publishing Group; Nature; 411; 6836; 5-2001; 480-484
0028-0836
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/35078085
info:eu-repo/semantics/altIdentifier/doi/10.1038/35078085
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 12.993085

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