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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/234330
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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 Técnicas2025-09-29T10:32:50Zoai: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:34982025-09-29 10:32:50.446CONICET 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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13.070432 |