Obesity-programmed mice are rescued by early genetic intervention

Autores
Bumaschny, Viviana Florencia; Yamashita, Miho; Casas Cordero, Rodrigo; Otero Corchón, Verónica; Silva Junqueira de Souza, Flavio; Rubinstein, Marcelo; Low, Malcolm J.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity.
Fil: Bumaschny, Viviana Florencia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Yamashita, Miho. University of Michigan; Estados Unidos
Fil: Casas Cordero, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Otero Corchón, Verónica. University of Michigan; Estados Unidos
Fil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Low, Malcolm J.. University of Michigan; Estados Unidos
Materia
OBESITY
PROOPIOMELANOCORTIN
FOOD INTAKE
MUTANT MOUSE
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:11336/272896
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Obesity-programmed mice are rescued by early genetic interventionBumaschny, Viviana FlorenciaYamashita, MihoCasas Cordero, RodrigoOtero Corchón, VerónicaSilva Junqueira de Souza, FlavioRubinstein, MarceloLow, Malcolm J.OBESITYPROOPIOMELANOCORTINFOOD INTAKEMUTANT MOUSEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity.Fil: Bumaschny, Viviana Florencia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Yamashita, Miho. University of Michigan; Estados UnidosFil: Casas Cordero, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Otero Corchón, Verónica. University of Michigan; Estados UnidosFil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Low, Malcolm J.. University of Michigan; Estados UnidosAmerican Society for Clinical Investigation2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/272896Bumaschny, Viviana Florencia; Yamashita, Miho; Casas Cordero, Rodrigo; Otero Corchón, Verónica; Silva Junqueira de Souza, Flavio; et al.; Obesity-programmed mice are rescued by early genetic intervention; American Society for Clinical Investigation; Journal of Clinical Investigation; 122; 11; 10-2012; 4203-42120021-9738CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/62543info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI62543info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T11:22:23Zoai:ri.conicet.gov.ar:11336/272896instacron: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:34982025-10-29 11:22:24.283CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Obesity-programmed mice are rescued by early genetic intervention
title Obesity-programmed mice are rescued by early genetic intervention
spellingShingle Obesity-programmed mice are rescued by early genetic intervention
Bumaschny, Viviana Florencia
OBESITY
PROOPIOMELANOCORTIN
FOOD INTAKE
MUTANT MOUSE
title_short Obesity-programmed mice are rescued by early genetic intervention
title_full Obesity-programmed mice are rescued by early genetic intervention
title_fullStr Obesity-programmed mice are rescued by early genetic intervention
title_full_unstemmed Obesity-programmed mice are rescued by early genetic intervention
title_sort Obesity-programmed mice are rescued by early genetic intervention
dc.creator.none.fl_str_mv Bumaschny, Viviana Florencia
Yamashita, Miho
Casas Cordero, Rodrigo
Otero Corchón, Verónica
Silva Junqueira de Souza, Flavio
Rubinstein, Marcelo
Low, Malcolm J.
author Bumaschny, Viviana Florencia
author_facet Bumaschny, Viviana Florencia
Yamashita, Miho
Casas Cordero, Rodrigo
Otero Corchón, Verónica
Silva Junqueira de Souza, Flavio
Rubinstein, Marcelo
Low, Malcolm J.
author_role author
author2 Yamashita, Miho
Casas Cordero, Rodrigo
Otero Corchón, Verónica
Silva Junqueira de Souza, Flavio
Rubinstein, Marcelo
Low, Malcolm J.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv OBESITY
PROOPIOMELANOCORTIN
FOOD INTAKE
MUTANT MOUSE
topic OBESITY
PROOPIOMELANOCORTIN
FOOD INTAKE
MUTANT MOUSE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity.
Fil: Bumaschny, Viviana Florencia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Yamashita, Miho. University of Michigan; Estados Unidos
Fil: Casas Cordero, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Otero Corchón, Verónica. University of Michigan; Estados Unidos
Fil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Low, Malcolm J.. University of Michigan; Estados Unidos
description Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
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/11336/272896
Bumaschny, Viviana Florencia; Yamashita, Miho; Casas Cordero, Rodrigo; Otero Corchón, Verónica; Silva Junqueira de Souza, Flavio; et al.; Obesity-programmed mice are rescued by early genetic intervention; American Society for Clinical Investigation; Journal of Clinical Investigation; 122; 11; 10-2012; 4203-4212
0021-9738
CONICET Digital
CONICET
url http://hdl.handle.net/11336/272896
identifier_str_mv Bumaschny, Viviana Florencia; Yamashita, Miho; Casas Cordero, Rodrigo; Otero Corchón, Verónica; Silva Junqueira de Souza, Flavio; et al.; Obesity-programmed mice are rescued by early genetic intervention; American Society for Clinical Investigation; Journal of Clinical Investigation; 122; 11; 10-2012; 4203-4212
0021-9738
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.jci.org/articles/view/62543
info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI62543
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
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 13.10058

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