Neurochemical characterization of brainstem pro-opiomelanocortin cells

Autores
Georgescu, Teodora; Lyons, David; Doslikova, Barbora; García, Ana Paula; Marston, Oliver; Burke, Luke K.; Chianese, Raffaella; Lam, Brian Y.H.; Yeo, Giles S.H.; Rochford, Justin J.; Garfield, Alastair S.; Heisler, Lora K.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity.
Fil: Georgescu, Teodora. University of Aberdeen; Reino Unido. University of Cambridge; Reino Unido. University of Otago; Nueva Zelanda
Fil: Lyons, David. University Of Aberdeeen; Reino Unido
Fil: Doslikova, Barbora. University of Cambridge; Reino Unido
Fil: García, Ana Paula. University of Cambridge; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina
Fil: Marston, Oliver. University of Cambridge; Reino Unido
Fil: Burke, Luke K.. University of Cambridge; Reino Unido
Fil: Chianese, Raffaella. University Of Aberdeeen; Reino Unido
Fil: Lam, Brian Y.H.. University of Cambridge; Reino Unido
Fil: Yeo, Giles S.H.. University of Cambridge; Reino Unido
Fil: Rochford, Justin J.. University of Cambridge; Reino Unido
Fil: Garfield, Alastair S.. University of Cambridge; Reino Unido
Fil: Heisler, Lora K.. University of Cambridge; Reino Unido. University Of Aberdeeen; Reino Unido
Materia
LEPTIN RECEPTOR
NTS
OBESITY
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:11336/139183

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oai_identifier_str oai:ri.conicet.gov.ar:11336/139183
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neurochemical characterization of brainstem pro-opiomelanocortin cellsGeorgescu, TeodoraLyons, DavidDoslikova, BarboraGarcía, Ana PaulaMarston, OliverBurke, Luke K.Chianese, RaffaellaLam, Brian Y.H.Yeo, Giles S.H.Rochford, Justin J.Garfield, Alastair S.Heisler, Lora K.LEPTIN RECEPTORNTSOBESITYPOMChttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity.Fil: Georgescu, Teodora. University of Aberdeen; Reino Unido. University of Cambridge; Reino Unido. University of Otago; Nueva ZelandaFil: Lyons, David. University Of Aberdeeen; Reino UnidoFil: Doslikova, Barbora. University of Cambridge; Reino UnidoFil: García, Ana Paula. University of Cambridge; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; ArgentinaFil: Marston, Oliver. University of Cambridge; Reino UnidoFil: Burke, Luke K.. University of Cambridge; Reino UnidoFil: Chianese, Raffaella. University Of Aberdeeen; Reino UnidoFil: Lam, Brian Y.H.. University of Cambridge; Reino UnidoFil: Yeo, Giles S.H.. University of Cambridge; Reino UnidoFil: Rochford, Justin J.. University of Cambridge; Reino UnidoFil: Garfield, Alastair S.. University of Cambridge; Reino UnidoFil: Heisler, Lora K.. University of Cambridge; Reino Unido. University Of Aberdeeen; Reino UnidoEndocrine Society2020-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/139183Georgescu, Teodora; Lyons, David; Doslikova, Barbora; García, Ana Paula; Marston, Oliver; et al.; Neurochemical characterization of brainstem pro-opiomelanocortin cells; Endocrine Society; Endocrinology; 161; 4; 4-2020; 1-130013-7227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1210/endocr/bqaa032info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/161/4/bqaa032/5804227info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:54Zoai:ri.conicet.gov.ar:11336/139183instacron: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 09:59:54.563CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neurochemical characterization of brainstem pro-opiomelanocortin cells
title Neurochemical characterization of brainstem pro-opiomelanocortin cells
spellingShingle Neurochemical characterization of brainstem pro-opiomelanocortin cells
Georgescu, Teodora
LEPTIN RECEPTOR
NTS
OBESITY
POMC
title_short Neurochemical characterization of brainstem pro-opiomelanocortin cells
title_full Neurochemical characterization of brainstem pro-opiomelanocortin cells
title_fullStr Neurochemical characterization of brainstem pro-opiomelanocortin cells
title_full_unstemmed Neurochemical characterization of brainstem pro-opiomelanocortin cells
title_sort Neurochemical characterization of brainstem pro-opiomelanocortin cells
dc.creator.none.fl_str_mv Georgescu, Teodora
Lyons, David
Doslikova, Barbora
García, Ana Paula
Marston, Oliver
Burke, Luke K.
Chianese, Raffaella
Lam, Brian Y.H.
Yeo, Giles S.H.
Rochford, Justin J.
Garfield, Alastair S.
Heisler, Lora K.
author Georgescu, Teodora
author_facet Georgescu, Teodora
Lyons, David
Doslikova, Barbora
García, Ana Paula
Marston, Oliver
Burke, Luke K.
Chianese, Raffaella
Lam, Brian Y.H.
Yeo, Giles S.H.
Rochford, Justin J.
Garfield, Alastair S.
Heisler, Lora K.
author_role author
author2 Lyons, David
Doslikova, Barbora
García, Ana Paula
Marston, Oliver
Burke, Luke K.
Chianese, Raffaella
Lam, Brian Y.H.
Yeo, Giles S.H.
Rochford, Justin J.
Garfield, Alastair S.
Heisler, Lora K.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LEPTIN RECEPTOR
NTS
OBESITY
POMC
topic LEPTIN RECEPTOR
NTS
OBESITY
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 Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity.
Fil: Georgescu, Teodora. University of Aberdeen; Reino Unido. University of Cambridge; Reino Unido. University of Otago; Nueva Zelanda
Fil: Lyons, David. University Of Aberdeeen; Reino Unido
Fil: Doslikova, Barbora. University of Cambridge; Reino Unido
Fil: García, Ana Paula. University of Cambridge; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina
Fil: Marston, Oliver. University of Cambridge; Reino Unido
Fil: Burke, Luke K.. University of Cambridge; Reino Unido
Fil: Chianese, Raffaella. University Of Aberdeeen; Reino Unido
Fil: Lam, Brian Y.H.. University of Cambridge; Reino Unido
Fil: Yeo, Giles S.H.. University of Cambridge; Reino Unido
Fil: Rochford, Justin J.. University of Cambridge; Reino Unido
Fil: Garfield, Alastair S.. University of Cambridge; Reino Unido
Fil: Heisler, Lora K.. University of Cambridge; Reino Unido. University Of Aberdeeen; Reino Unido
description Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity.
publishDate 2020
dc.date.none.fl_str_mv 2020-04
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/11336/139183
Georgescu, Teodora; Lyons, David; Doslikova, Barbora; García, Ana Paula; Marston, Oliver; et al.; Neurochemical characterization of brainstem pro-opiomelanocortin cells; Endocrine Society; Endocrinology; 161; 4; 4-2020; 1-13
0013-7227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/139183
identifier_str_mv Georgescu, Teodora; Lyons, David; Doslikova, Barbora; García, Ana Paula; Marston, Oliver; et al.; Neurochemical characterization of brainstem pro-opiomelanocortin cells; Endocrine Society; Endocrinology; 161; 4; 4-2020; 1-13
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/endocr/bqaa032
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/161/4/bqaa032/5804227
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
application/pdf
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
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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