Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons

Autores
Hael, Clara Ercilia; Rubinstein, Marcelo
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Although it is well accepted that the adipostatic hormone leptin activates Pomc expression inhypothalamic neurons, the mechanisms controlling this interaction remain unexplored. In thebrain, leptin binds to the long form of the leptin receptor stimulating the intracellularphosphorylation of STAT3 which acts as a transcription factor of several genes by acting on STAT3binding motifs. We have detected that the neuronal Pomc enhancer 1 (nPE1) contains twocanonical STAT3 binding motifs (5?-TTCCNGGAA-3?) which are highly conserved in mammals. Tochallenge the hypothesis that these sites participate in leptin´s induced Pomc expression wegenerated mutant mice lacking both STAT3 sites from nPE1 using CRISPR/Cas9 technology. Tomaximize leptin´s effect on hypothalamic Pomc expression we previously reduced circulatingleptin levels using two different experimental strategies. Our first approach was to study the effectof refeeding on mice previously fasted for 24 h and analyze body weight variations andhypothalamic Pomc mRNA levels. Our preliminary results indicate a greater weight loss in micelacking STAT3 sites after fasting and a more rapid regain of previous body weight. The secondapproach involves crossing nPE1(STAT3-less) mice with leptin-deficient (ob/ob) mice. Furtherprogress of these experiments will give us the possibility to evaluate the implication of STAT3binding sites in the regulation of hypothalamic expression of POMC induced by leptin.
Fil: Hael, Clara Ercilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Rubinstein, Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
XXXIII Congress of the Argentine Society for Research in Neuroscience
Cordoba
Argentina
Sociedad Argentina de Investigaciones en Neurociencias
Materia
PROOPIOMELANOCORTIN
LEPTIN
STAT3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/234330
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic NeuronsHael, Clara ErciliaRubinstein, MarceloPROOPIOMELANOCORTINLEPTINSTAT3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Although it is well accepted that the adipostatic hormone leptin activates Pomc expression inhypothalamic neurons, the mechanisms controlling this interaction remain unexplored. In thebrain, leptin binds to the long form of the leptin receptor stimulating the intracellularphosphorylation of STAT3 which acts as a transcription factor of several genes by acting on STAT3binding motifs. We have detected that the neuronal Pomc enhancer 1 (nPE1) contains twocanonical STAT3 binding motifs (5?-TTCCNGGAA-3?) which are highly conserved in mammals. Tochallenge the hypothesis that these sites participate in leptin´s induced Pomc expression wegenerated mutant mice lacking both STAT3 sites from nPE1 using CRISPR/Cas9 technology. Tomaximize leptin´s effect on hypothalamic Pomc expression we previously reduced circulatingleptin levels using two different experimental strategies. Our first approach was to study the effectof refeeding on mice previously fasted for 24 h and analyze body weight variations andhypothalamic Pomc mRNA levels. Our preliminary results indicate a greater weight loss in micelacking STAT3 sites after fasting and a more rapid regain of previous body weight. The secondapproach involves crossing nPE1(STAT3-less) mice with leptin-deficient (ob/ob) mice. Furtherprogress of these experiments will give us the possibility to evaluate the implication of STAT3binding sites in the regulation of hypothalamic expression of POMC induced by leptin.Fil: Hael, Clara Ercilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Rubinstein, Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaXXXIII Congress of the Argentine Society for Research in NeuroscienceCordobaArgentinaSociedad Argentina de Investigaciones en NeurocienciasSAGE Publications2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/234330Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons; XXXIII Congress of the Argentine Society for Research in Neuroscience; Cordoba; Argentina; 2018; 50-501759-09141759-0914CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://doi.org/10.1177/1759091419834821Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:30:15Zoai:ri.conicet.gov.ar:11336/234330instacron: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:34982025-10-15 15:30:15.358CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
title Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
spellingShingle Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
Hael, Clara Ercilia
PROOPIOMELANOCORTIN
LEPTIN
STAT3
title_short Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
title_full Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
title_fullStr Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
title_full_unstemmed Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
title_sort Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons
dc.creator.none.fl_str_mv Hael, Clara Ercilia
Rubinstein, Marcelo
author Hael, Clara Ercilia
author_facet Hael, Clara Ercilia
Rubinstein, Marcelo
author_role author
author2 Rubinstein, Marcelo
author2_role author
dc.subject.none.fl_str_mv PROOPIOMELANOCORTIN
LEPTIN
STAT3
topic PROOPIOMELANOCORTIN
LEPTIN
STAT3
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Although it is well accepted that the adipostatic hormone leptin activates Pomc expression inhypothalamic neurons, the mechanisms controlling this interaction remain unexplored. In thebrain, leptin binds to the long form of the leptin receptor stimulating the intracellularphosphorylation of STAT3 which acts as a transcription factor of several genes by acting on STAT3binding motifs. We have detected that the neuronal Pomc enhancer 1 (nPE1) contains twocanonical STAT3 binding motifs (5?-TTCCNGGAA-3?) which are highly conserved in mammals. Tochallenge the hypothesis that these sites participate in leptin´s induced Pomc expression wegenerated mutant mice lacking both STAT3 sites from nPE1 using CRISPR/Cas9 technology. Tomaximize leptin´s effect on hypothalamic Pomc expression we previously reduced circulatingleptin levels using two different experimental strategies. Our first approach was to study the effectof refeeding on mice previously fasted for 24 h and analyze body weight variations andhypothalamic Pomc mRNA levels. Our preliminary results indicate a greater weight loss in micelacking STAT3 sites after fasting and a more rapid regain of previous body weight. The secondapproach involves crossing nPE1(STAT3-less) mice with leptin-deficient (ob/ob) mice. Furtherprogress of these experiments will give us the possibility to evaluate the implication of STAT3binding sites in the regulation of hypothalamic expression of POMC induced by leptin.
Fil: Hael, Clara Ercilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Rubinstein, Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
XXXIII Congress of the Argentine Society for Research in Neuroscience
Cordoba
Argentina
Sociedad Argentina de Investigaciones en Neurociencias
description Although it is well accepted that the adipostatic hormone leptin activates Pomc expression inhypothalamic neurons, the mechanisms controlling this interaction remain unexplored. In thebrain, leptin binds to the long form of the leptin receptor stimulating the intracellularphosphorylation of STAT3 which acts as a transcription factor of several genes by acting on STAT3binding motifs. We have detected that the neuronal Pomc enhancer 1 (nPE1) contains twocanonical STAT3 binding motifs (5?-TTCCNGGAA-3?) which are highly conserved in mammals. Tochallenge the hypothesis that these sites participate in leptin´s induced Pomc expression wegenerated mutant mice lacking both STAT3 sites from nPE1 using CRISPR/Cas9 technology. Tomaximize leptin´s effect on hypothalamic Pomc expression we previously reduced circulatingleptin levels using two different experimental strategies. Our first approach was to study the effectof refeeding on mice previously fasted for 24 h and analyze body weight variations andhypothalamic Pomc mRNA levels. Our preliminary results indicate a greater weight loss in micelacking STAT3 sites after fasting and a more rapid regain of previous body weight. The secondapproach involves crossing nPE1(STAT3-less) mice with leptin-deficient (ob/ob) mice. Furtherprogress of these experiments will give us the possibility to evaluate the implication of STAT3binding sites in the regulation of hypothalamic expression of POMC induced by leptin.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/234330
Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons; XXXIII Congress of the Argentine Society for Research in Neuroscience; Cordoba; Argentina; 2018; 50-50
1759-0914
1759-0914
CONICET Digital
CONICET
url http://hdl.handle.net/11336/234330
identifier_str_mv Leptin-Mediated Transcriptional Regulation of Pomc in Hypothalamic Neurons; XXXIII Congress of the Argentine Society for Research in Neuroscience; Cordoba; Argentina; 2018; 50-50
1759-0914
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://doi.org/10.1177/1759091419834821
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv SAGE Publications
publisher.none.fl_str_mv SAGE Publications
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 13.22299

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