Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity

Autores
Friend, Danielle M.; Devarakonda, Kavya; O'Neal, Timothy J.; Skirzewski, Miguel; Papageorgiou, Ioannis; Kaplan, Alanna R.; Liow, Jeih San; Guo, Juen; Rane, Sushil G.; Rubinstein, Marcelo; Alvarez, Verónica A.; Hall, Kevin D.; Kravitz, Alexxai V.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.
Fil: Friend, Danielle M.. National Institutes of Health; Estados Unidos
Fil: Devarakonda, Kavya. National Institutes of Health; Estados Unidos
Fil: O'Neal, Timothy J.. National Institutes of Health; Estados Unidos
Fil: Skirzewski, Miguel. National Institutes of Health; Estados Unidos
Fil: Papageorgiou, Ioannis. National Institutes of Health; Estados Unidos
Fil: Kaplan, Alanna R.. National Institutes of Health; Estados Unidos
Fil: Liow, Jeih San. National Institutes of Health; Estados Unidos
Fil: Guo, Juen. National Institutes of Health; Estados Unidos
Fil: Rane, Sushil G.. National Institutes of Health; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. University of Michigan; Estados Unidos
Fil: Alvarez, Verónica A.. National Institutes of Health; Estados Unidos
Fil: Hall, Kevin D.. National Institutes of Health; Estados Unidos
Fil: Kravitz, Alexxai V.. National Institutes of Health; Estados Unidos
Materia
D2
Dopamine
Exercise
Obese
Obesity
Physical Activity
Striatum
Weight Loss
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:11336/40852
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/40852
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Basal Ganglia Dysfunction Contributes to Physical Inactivity in ObesityFriend, Danielle M.Devarakonda, KavyaO'Neal, Timothy J.Skirzewski, MiguelPapageorgiou, IoannisKaplan, Alanna R.Liow, Jeih SanGuo, JuenRane, Sushil G.Rubinstein, MarceloAlvarez, Verónica A.Hall, Kevin D.Kravitz, Alexxai V.D2DopamineExerciseObeseObesityPhysical ActivityStriatumWeight Losshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.Fil: Friend, Danielle M.. National Institutes of Health; Estados UnidosFil: Devarakonda, Kavya. National Institutes of Health; Estados UnidosFil: O'Neal, Timothy J.. National Institutes of Health; Estados UnidosFil: Skirzewski, Miguel. National Institutes of Health; Estados UnidosFil: Papageorgiou, Ioannis. National Institutes of Health; Estados UnidosFil: Kaplan, Alanna R.. National Institutes of Health; Estados UnidosFil: Liow, Jeih San. National Institutes of Health; Estados UnidosFil: Guo, Juen. National Institutes of Health; Estados UnidosFil: Rane, Sushil G.. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. University of Michigan; Estados UnidosFil: Alvarez, Verónica A.. National Institutes of Health; Estados UnidosFil: Hall, Kevin D.. National Institutes of Health; Estados UnidosFil: Kravitz, Alexxai V.. National Institutes of Health; Estados UnidosCell Press2017-02info: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/11336/40852Friend, Danielle M.; Devarakonda, Kavya; O'Neal, Timothy J.; Skirzewski, Miguel; Papageorgiou, Ioannis; et al.; Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity; Cell Press; Cell Metabolism; 25; 2; 2-2017; 312-3211550-4131CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2016.12.001info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30596-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:46:10Zoai:ri.conicet.gov.ar:11336/40852instacron: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 10:46:11.16CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
title Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
spellingShingle Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
Friend, Danielle M.
D2
Dopamine
Exercise
Obese
Obesity
Physical Activity
Striatum
Weight Loss
title_short Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
title_full Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
title_fullStr Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
title_full_unstemmed Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
title_sort Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
dc.creator.none.fl_str_mv Friend, Danielle M.
Devarakonda, Kavya
O'Neal, Timothy J.
Skirzewski, Miguel
Papageorgiou, Ioannis
Kaplan, Alanna R.
Liow, Jeih San
Guo, Juen
Rane, Sushil G.
Rubinstein, Marcelo
Alvarez, Verónica A.
Hall, Kevin D.
Kravitz, Alexxai V.
author Friend, Danielle M.
author_facet Friend, Danielle M.
Devarakonda, Kavya
O'Neal, Timothy J.
Skirzewski, Miguel
Papageorgiou, Ioannis
Kaplan, Alanna R.
Liow, Jeih San
Guo, Juen
Rane, Sushil G.
Rubinstein, Marcelo
Alvarez, Verónica A.
Hall, Kevin D.
Kravitz, Alexxai V.
author_role author
author2 Devarakonda, Kavya
O'Neal, Timothy J.
Skirzewski, Miguel
Papageorgiou, Ioannis
Kaplan, Alanna R.
Liow, Jeih San
Guo, Juen
Rane, Sushil G.
Rubinstein, Marcelo
Alvarez, Verónica A.
Hall, Kevin D.
Kravitz, Alexxai V.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv D2
Dopamine
Exercise
Obese
Obesity
Physical Activity
Striatum
Weight Loss
topic D2
Dopamine
Exercise
Obese
Obesity
Physical Activity
Striatum
Weight Loss
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.
Fil: Friend, Danielle M.. National Institutes of Health; Estados Unidos
Fil: Devarakonda, Kavya. National Institutes of Health; Estados Unidos
Fil: O'Neal, Timothy J.. National Institutes of Health; Estados Unidos
Fil: Skirzewski, Miguel. National Institutes of Health; Estados Unidos
Fil: Papageorgiou, Ioannis. National Institutes of Health; Estados Unidos
Fil: Kaplan, Alanna R.. National Institutes of Health; Estados Unidos
Fil: Liow, Jeih San. National Institutes of Health; Estados Unidos
Fil: Guo, Juen. National Institutes of Health; Estados Unidos
Fil: Rane, Sushil G.. National Institutes of Health; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. University of Michigan; Estados Unidos
Fil: Alvarez, Verónica A.. National Institutes of Health; Estados Unidos
Fil: Hall, Kevin D.. National Institutes of Health; Estados Unidos
Fil: Kravitz, Alexxai V.. National Institutes of Health; Estados Unidos
description Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.
publishDate 2017
dc.date.none.fl_str_mv 2017-02
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/11336/40852
Friend, Danielle M.; Devarakonda, Kavya; O'Neal, Timothy J.; Skirzewski, Miguel; Papageorgiou, Ioannis; et al.; Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity; Cell Press; Cell Metabolism; 25; 2; 2-2017; 312-321
1550-4131
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40852
identifier_str_mv Friend, Danielle M.; Devarakonda, Kavya; O'Neal, Timothy J.; Skirzewski, Miguel; Papageorgiou, Ioannis; et al.; Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity; Cell Press; Cell Metabolism; 25; 2; 2-2017; 312-321
1550-4131
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2016.12.001
info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30596-4
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 Cell Press
publisher.none.fl_str_mv Cell Press
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 13.070432

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