Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing

Autores
Cakir, Isin; Cyr, Nicole E.; Perello, Mario; Litvinov, Bogdan Patedakis; Romero, Amparo; Stuart, Ronald C.; Nillni, Eduardo A.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.
Fil: Cakir, Isin. Brown University; Estados Unidos
Fil: Cyr, Nicole E.. Brown University; Estados Unidos
Fil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Litvinov, Bogdan Patedakis. Brown University; Estados Unidos
Fil: Romero, Amparo. Brown University; Estados Unidos
Fil: Stuart, Ronald C.. Brown University; Estados Unidos
Fil: Nillni, Eduardo A.. Brown University; Estados Unidos
Materia
Hypothalamus
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:11336/24511

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network_name_str CONICET Digital (CONICET)
spelling Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational ProcessingCakir, IsinCyr, Nicole E.Perello, MarioLitvinov, Bogdan PatedakisRomero, AmparoStuart, Ronald C.Nillni, Eduardo A.HypothalamusobesityPOMChttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.Fil: Cakir, Isin. Brown University; Estados UnidosFil: Cyr, Nicole E.. Brown University; Estados UnidosFil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Litvinov, Bogdan Patedakis. Brown University; Estados UnidosFil: Romero, Amparo. Brown University; Estados UnidosFil: Stuart, Ronald C.. Brown University; Estados UnidosFil: Nillni, Eduardo A.. Brown University; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24511Cakir, Isin; Cyr, Nicole E.; Perello, Mario; Litvinov, Bogdan Patedakis; Romero, Amparo; et al.; Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 288; 6-2013; 17675-176880021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/288/24/17675.fullinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M113.475343info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:26Zoai:ri.conicet.gov.ar:11336/24511instacron: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 09:49:26.908CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
title Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
spellingShingle Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
Cakir, Isin
Hypothalamus
obesity
POMC
title_short Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
title_full Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
title_fullStr Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
title_full_unstemmed Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
title_sort Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing
dc.creator.none.fl_str_mv Cakir, Isin
Cyr, Nicole E.
Perello, Mario
Litvinov, Bogdan Patedakis
Romero, Amparo
Stuart, Ronald C.
Nillni, Eduardo A.
author Cakir, Isin
author_facet Cakir, Isin
Cyr, Nicole E.
Perello, Mario
Litvinov, Bogdan Patedakis
Romero, Amparo
Stuart, Ronald C.
Nillni, Eduardo A.
author_role author
author2 Cyr, Nicole E.
Perello, Mario
Litvinov, Bogdan Patedakis
Romero, Amparo
Stuart, Ronald C.
Nillni, Eduardo A.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Hypothalamus
obesity
POMC
topic Hypothalamus
obesity
POMC
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 was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.
Fil: Cakir, Isin. Brown University; Estados Unidos
Fil: Cyr, Nicole E.. Brown University; Estados Unidos
Fil: Perello, Mario. Brown University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Litvinov, Bogdan Patedakis. Brown University; Estados Unidos
Fil: Romero, Amparo. Brown University; Estados Unidos
Fil: Stuart, Ronald C.. Brown University; Estados Unidos
Fil: Nillni, Eduardo A.. Brown University; Estados Unidos
description It was shown previously that abnormal prohormone processing or inactive proconverting enzymes that are responsible for this processing cause profound obesity. Our laboratory demonstrated earlier that in the diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide -melanocyte-stimulating hormone ( -MSH) is reduced, yet the mRNA of its precursor protein proopiomelanocortin (POMC) remained unaltered. It was also shown that the DIO condition promotes the development of endoplasmic reticulum (ER) stress and leptin resistance. In the current study, using an in vivo model combined with in vitro experiments, we demonstrate that obesity-induced ER stress obstructs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyzes the conversion of adrenocorticotropin to -MSH, thereby decreasing -MSH peptide production. This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER stress in regulating central energy balance in obesity.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/24511
Cakir, Isin; Cyr, Nicole E.; Perello, Mario; Litvinov, Bogdan Patedakis; Romero, Amparo; et al.; Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 288; 6-2013; 17675-17688
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24511
identifier_str_mv Cakir, Isin; Cyr, Nicole E.; Perello, Mario; Litvinov, Bogdan Patedakis; Romero, Amparo; et al.; Obesity Induces Hypothalamic Endoplasmic Reticulum Stress and Impairs Proopiomelanocortin (POMC) Post-translational Processing; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 288; 6-2013; 17675-17688
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/288/24/17675.full
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M113.475343
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 American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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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