Central serotonin and melanocortin pathways regulating energy homeostasis

Autores
Heisler, Lora K.; Cowley, Michael A.; Kishi, Toshiro; Tecott, Laurence H.; Fan, Wei; Low, Malcolm J.; Smart, James L.; Rubinstein, Marcelo; Tatro, Jeffrey B.; Zigman, Jeffrey M.; Cone, Roger D.; Elmquist, Joel K.
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which central serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT2CR) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus.
Fil: Heisler, Lora K.. Harvard Medical School; Estados Unidos
Fil: Cowley, Michael A.. Oregon Health and Science University; Estados Unidos
Fil: Kishi, Toshiro. Harvard Medical School; Estados Unidos
Fil: Tecott, Laurence H.. University of California; Estados Unidos
Fil: Fan, Wei. Oregon Health and Science University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Smart, James L.. 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: Tatro, Jeffrey B.. Tufts University School of Medicine; Estados Unidos
Fil: Zigman, Jeffrey M.. Harvard Medical School; Estados Unidos
Fil: Cone, Roger D.. Oregon Health and Science University; Estados Unidos
Fil: Elmquist, Joel K.. Harvard Medical School; Estados Unidos
Materia
And Arcuate Nucleus
Body Weight
Food Intake
Hypothalamus
Melanocortin
Melanocortin 4 Receptor (Mc4-R)
Pro-Opiomelanocortin (Pomc)
Serotonin
Serotonin 2c Receptor (5-Ht2cr)
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:11336/79832
Acceder
id CONICETDig_2c5bb8c59d7a209777b4d7dfdff4f56e
oai_identifier_str oai:ri.conicet.gov.ar:11336/79832
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Central serotonin and melanocortin pathways regulating energy homeostasisHeisler, Lora K.Cowley, Michael A.Kishi, ToshiroTecott, Laurence H.Fan, WeiLow, Malcolm J.Smart, James L.Rubinstein, MarceloTatro, Jeffrey B.Zigman, Jeffrey M.Cone, Roger D.Elmquist, Joel K.And Arcuate NucleusBody WeightFood IntakeHypothalamusMelanocortinMelanocortin 4 Receptor (Mc4-R)Pro-Opiomelanocortin (Pomc)SerotoninSerotonin 2c Receptor (5-Ht2cr)https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which central serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT2CR) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus.Fil: Heisler, Lora K.. Harvard Medical School; Estados UnidosFil: Cowley, Michael A.. Oregon Health and Science University; Estados UnidosFil: Kishi, Toshiro. Harvard Medical School; Estados UnidosFil: Tecott, Laurence H.. University of California; Estados UnidosFil: Fan, Wei. Oregon Health and Science University; Estados UnidosFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Smart, James L.. 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: Tatro, Jeffrey B.. Tufts University School of Medicine; Estados UnidosFil: Zigman, Jeffrey M.. Harvard Medical School; Estados UnidosFil: Cone, Roger D.. Oregon Health and Science University; Estados UnidosFil: Elmquist, Joel K.. Harvard Medical School; Estados UnidosThe New York Academy of Sciences2003-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79832Heisler, Lora K.; Cowley, Michael A.; Kishi, Toshiro; Tecott, Laurence H.; Fan, Wei; et al.; Central serotonin and melanocortin pathways regulating energy homeostasis; The New York Academy of Sciences; Annals of the New York Academy of Sciences; 994; 6-2003; 169-1740077-8923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12851313info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1749-6632.2003.tb03177.xinfo:eu-repo/semantics/altIdentifier/url/https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2003.tb03177.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:17Zoai:ri.conicet.gov.ar:11336/79832instacron: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 10:14:17.567CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Central serotonin and melanocortin pathways regulating energy homeostasis
title Central serotonin and melanocortin pathways regulating energy homeostasis
spellingShingle Central serotonin and melanocortin pathways regulating energy homeostasis
Heisler, Lora K.
And Arcuate Nucleus
Body Weight
Food Intake
Hypothalamus
Melanocortin
Melanocortin 4 Receptor (Mc4-R)
Pro-Opiomelanocortin (Pomc)
Serotonin
Serotonin 2c Receptor (5-Ht2cr)
title_short Central serotonin and melanocortin pathways regulating energy homeostasis
title_full Central serotonin and melanocortin pathways regulating energy homeostasis
title_fullStr Central serotonin and melanocortin pathways regulating energy homeostasis
title_full_unstemmed Central serotonin and melanocortin pathways regulating energy homeostasis
title_sort Central serotonin and melanocortin pathways regulating energy homeostasis
dc.creator.none.fl_str_mv Heisler, Lora K.
Cowley, Michael A.
Kishi, Toshiro
Tecott, Laurence H.
Fan, Wei
Low, Malcolm J.
Smart, James L.
Rubinstein, Marcelo
Tatro, Jeffrey B.
Zigman, Jeffrey M.
Cone, Roger D.
Elmquist, Joel K.
author Heisler, Lora K.
author_facet Heisler, Lora K.
Cowley, Michael A.
Kishi, Toshiro
Tecott, Laurence H.
Fan, Wei
Low, Malcolm J.
Smart, James L.
Rubinstein, Marcelo
Tatro, Jeffrey B.
Zigman, Jeffrey M.
Cone, Roger D.
Elmquist, Joel K.
author_role author
author2 Cowley, Michael A.
Kishi, Toshiro
Tecott, Laurence H.
Fan, Wei
Low, Malcolm J.
Smart, James L.
Rubinstein, Marcelo
Tatro, Jeffrey B.
Zigman, Jeffrey M.
Cone, Roger D.
Elmquist, Joel K.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv And Arcuate Nucleus
Body Weight
Food Intake
Hypothalamus
Melanocortin
Melanocortin 4 Receptor (Mc4-R)
Pro-Opiomelanocortin (Pomc)
Serotonin
Serotonin 2c Receptor (5-Ht2cr)
topic And Arcuate Nucleus
Body Weight
Food Intake
Hypothalamus
Melanocortin
Melanocortin 4 Receptor (Mc4-R)
Pro-Opiomelanocortin (Pomc)
Serotonin
Serotonin 2c Receptor (5-Ht2cr)
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which central serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT2CR) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus.
Fil: Heisler, Lora K.. Harvard Medical School; Estados Unidos
Fil: Cowley, Michael A.. Oregon Health and Science University; Estados Unidos
Fil: Kishi, Toshiro. Harvard Medical School; Estados Unidos
Fil: Tecott, Laurence H.. University of California; Estados Unidos
Fil: Fan, Wei. Oregon Health and Science University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health and Science University; Estados Unidos
Fil: Smart, James L.. 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: Tatro, Jeffrey B.. Tufts University School of Medicine; Estados Unidos
Fil: Zigman, Jeffrey M.. Harvard Medical School; Estados Unidos
Fil: Cone, Roger D.. Oregon Health and Science University; Estados Unidos
Fil: Elmquist, Joel K.. Harvard Medical School; Estados Unidos
description It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which central serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT2CR) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus.
publishDate 2003
dc.date.none.fl_str_mv 2003-06
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/11336/79832
Heisler, Lora K.; Cowley, Michael A.; Kishi, Toshiro; Tecott, Laurence H.; Fan, Wei; et al.; Central serotonin and melanocortin pathways regulating energy homeostasis; The New York Academy of Sciences; Annals of the New York Academy of Sciences; 994; 6-2003; 169-174
0077-8923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79832
identifier_str_mv Heisler, Lora K.; Cowley, Michael A.; Kishi, Toshiro; Tecott, Laurence H.; Fan, Wei; et al.; Central serotonin and melanocortin pathways regulating energy homeostasis; The New York Academy of Sciences; Annals of the New York Academy of Sciences; 994; 6-2003; 169-174
0077-8923
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.ncbi.nlm.nih.gov/pubmed/12851313
info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1749-6632.2003.tb03177.x
info:eu-repo/semantics/altIdentifier/url/https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2003.tb03177.x
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 The New York Academy of Sciences
publisher.none.fl_str_mv The New York Academy of Sciences
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 13.069144

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