Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity

Autores
Leiss, Veronika; Schönsiegel, Annika; Gnad, Thorsten; Kerner, Johannes; Kaur, Jyotsna; Sartorius, Tina; Machann, Jürgen; Schick, Fritz; Birnbaumer, Lutz; Häring, Hans Ulrich; Pfeifer, Alexander; Nürnberg, Bernd
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: Typically, obesity results from an inappropriate balance between energy uptake from nutrient consumption and burning of calories, which leads to a pathological increase in fat mass. Obesity is a major cause of insulin resistance and diabetes. Inhibitory G proteins (Gαi) form a subfamily that is involved in the regulation of adipose tissue function. Among the three Gαi members, i.e. Gαi1, Gαi2, Gαi3, the Gαi2, protein is predominantly expressed in adipose tissue. However, the functions of the Gαi2 isoform in adipose tissue and its impact on the development of obesity are poorly understood. Methods: By using AdipoqCreERT2 mice, we generated adipocyte-specific Gnai2-deficient mice to study Gαi2 function, specifically in white and brown adipocytes. These mice were fed either a control diet (CD) or a high fat diet (HFD). Mice were examined for obesity development, insulin resistance and glucose intolerance. We examined adipocyte morphology and the development of inflammation in the white adipose tissue. Finally, intracellular cAMP levels as an indicator of Gαi signaling and glycerol release as an indicator of lipolysis rates were measured to verify the impact of Gαi2 on the signaling pathway in brown and white adipocytes. Results: An adipocyte-specific deficiency of Gαi2 significantly reduced diet-induced obesity, leading to decreased fat masses, smaller adipocytes and decreased inflammation in the white adipose tissue relative to littermate controls. Concurrently, oxygen consumption of brown adipocytes and in vivo measured energy expenditure were significantly enhanced. In addition, glucose tolerance and insulin sensitivity of HFD-fed adipocyte-specific Gnai2-deficient mice were improved compared to the respective controls. In the absence of Gαi2, adrenergic stimulation of intracellular adipocyte cAMP levels was increased, which correlated with increased lipolysis and energy expenditure. Conclusion: We conclude that adipocyte Gαi2 is a major regulator of adipocyte lipid content in diet-induced obesity by inhibiting adipocyte lipolysis in a cAMP-dependent manner resulting in increased energy expenditure.
Fil: Leiss, Veronika. Eberhard Karls Universität Tübingen; Alemania
Fil: Schönsiegel, Annika. Eberhard Karls Universität Tübingen; Alemania
Fil: Gnad, Thorsten. Universitat Bonn; Alemania
Fil: Kerner, Johannes. Eberhard Karls Universität Tübingen; Alemania
Fil: Kaur, Jyotsna. Eberhard Karls Universität Tübingen; Alemania
Fil: Sartorius, Tina. Eberhard Karls Universität Tübingen; Alemania
Fil: Machann, Jürgen. Eberhard Karls Universität Tübingen; Alemania
Fil: Schick, Fritz. Eberhard Karls Universität Tübingen; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Häring, Hans Ulrich. Eberhard Karls Universität Tübingen; Alemania
Fil: Pfeifer, Alexander. Universitat Bonn; Alemania
Fil: Nürnberg, Bernd. Eberhard Karls Universität Tübingen; Alemania
Materia
ADIPOCYTES
BROWN ADIPOSE TISSUE
G PROTEINS
GNAI2
HIGH FAT DIET
INSULIN
OBESITY
WHITE ADIPOSE TISSUE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/140621
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/140621
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesityLeiss, VeronikaSchönsiegel, AnnikaGnad, ThorstenKerner, JohannesKaur, JyotsnaSartorius, TinaMachann, JürgenSchick, FritzBirnbaumer, LutzHäring, Hans UlrichPfeifer, AlexanderNürnberg, BerndADIPOCYTESBROWN ADIPOSE TISSUEG PROTEINSGNAI2HIGH FAT DIETINSULINOBESITYWHITE ADIPOSE TISSUEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Objectives: Typically, obesity results from an inappropriate balance between energy uptake from nutrient consumption and burning of calories, which leads to a pathological increase in fat mass. Obesity is a major cause of insulin resistance and diabetes. Inhibitory G proteins (Gαi) form a subfamily that is involved in the regulation of adipose tissue function. Among the three Gαi members, i.e. Gαi1, Gαi2, Gαi3, the Gαi2, protein is predominantly expressed in adipose tissue. However, the functions of the Gαi2 isoform in adipose tissue and its impact on the development of obesity are poorly understood. Methods: By using AdipoqCreERT2 mice, we generated adipocyte-specific Gnai2-deficient mice to study Gαi2 function, specifically in white and brown adipocytes. These mice were fed either a control diet (CD) or a high fat diet (HFD). Mice were examined for obesity development, insulin resistance and glucose intolerance. We examined adipocyte morphology and the development of inflammation in the white adipose tissue. Finally, intracellular cAMP levels as an indicator of Gαi signaling and glycerol release as an indicator of lipolysis rates were measured to verify the impact of Gαi2 on the signaling pathway in brown and white adipocytes. Results: An adipocyte-specific deficiency of Gαi2 significantly reduced diet-induced obesity, leading to decreased fat masses, smaller adipocytes and decreased inflammation in the white adipose tissue relative to littermate controls. Concurrently, oxygen consumption of brown adipocytes and in vivo measured energy expenditure were significantly enhanced. In addition, glucose tolerance and insulin sensitivity of HFD-fed adipocyte-specific Gnai2-deficient mice were improved compared to the respective controls. In the absence of Gαi2, adrenergic stimulation of intracellular adipocyte cAMP levels was increased, which correlated with increased lipolysis and energy expenditure. Conclusion: We conclude that adipocyte Gαi2 is a major regulator of adipocyte lipid content in diet-induced obesity by inhibiting adipocyte lipolysis in a cAMP-dependent manner resulting in increased energy expenditure.Fil: Leiss, Veronika. Eberhard Karls Universität Tübingen; AlemaniaFil: Schönsiegel, Annika. Eberhard Karls Universität Tübingen; AlemaniaFil: Gnad, Thorsten. Universitat Bonn; AlemaniaFil: Kerner, Johannes. Eberhard Karls Universität Tübingen; AlemaniaFil: Kaur, Jyotsna. Eberhard Karls Universität Tübingen; AlemaniaFil: Sartorius, Tina. Eberhard Karls Universität Tübingen; AlemaniaFil: Machann, Jürgen. Eberhard Karls Universität Tübingen; AlemaniaFil: Schick, Fritz. Eberhard Karls Universität Tübingen; AlemaniaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Häring, Hans Ulrich. Eberhard Karls Universität Tübingen; AlemaniaFil: Pfeifer, Alexander. Universitat Bonn; AlemaniaFil: Nürnberg, Bernd. Eberhard Karls Universität Tübingen; AlemaniaElsevier2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140621Leiss, Veronika; Schönsiegel, Annika; Gnad, Thorsten; Kerner, Johannes; Kaur, Jyotsna; et al.; Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity; Elsevier; Molecular Metabolism; 40; 10-2020; 1-132212-8778CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.molmet.2020.101029info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2212877820301034?via%3Dihubinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:35:02Zoai:ri.conicet.gov.ar:11336/140621instacron: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 15:35:03.05CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
title Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
spellingShingle Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
Leiss, Veronika
ADIPOCYTES
BROWN ADIPOSE TISSUE
G PROTEINS
GNAI2
HIGH FAT DIET
INSULIN
OBESITY
WHITE ADIPOSE TISSUE
title_short Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
title_full Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
title_fullStr Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
title_full_unstemmed Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
title_sort Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity
dc.creator.none.fl_str_mv Leiss, Veronika
Schönsiegel, Annika
Gnad, Thorsten
Kerner, Johannes
Kaur, Jyotsna
Sartorius, Tina
Machann, Jürgen
Schick, Fritz
Birnbaumer, Lutz
Häring, Hans Ulrich
Pfeifer, Alexander
Nürnberg, Bernd
author Leiss, Veronika
author_facet Leiss, Veronika
Schönsiegel, Annika
Gnad, Thorsten
Kerner, Johannes
Kaur, Jyotsna
Sartorius, Tina
Machann, Jürgen
Schick, Fritz
Birnbaumer, Lutz
Häring, Hans Ulrich
Pfeifer, Alexander
Nürnberg, Bernd
author_role author
author2 Schönsiegel, Annika
Gnad, Thorsten
Kerner, Johannes
Kaur, Jyotsna
Sartorius, Tina
Machann, Jürgen
Schick, Fritz
Birnbaumer, Lutz
Häring, Hans Ulrich
Pfeifer, Alexander
Nürnberg, Bernd
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADIPOCYTES
BROWN ADIPOSE TISSUE
G PROTEINS
GNAI2
HIGH FAT DIET
INSULIN
OBESITY
WHITE ADIPOSE TISSUE
topic ADIPOCYTES
BROWN ADIPOSE TISSUE
G PROTEINS
GNAI2
HIGH FAT DIET
INSULIN
OBESITY
WHITE ADIPOSE TISSUE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Objectives: Typically, obesity results from an inappropriate balance between energy uptake from nutrient consumption and burning of calories, which leads to a pathological increase in fat mass. Obesity is a major cause of insulin resistance and diabetes. Inhibitory G proteins (Gαi) form a subfamily that is involved in the regulation of adipose tissue function. Among the three Gαi members, i.e. Gαi1, Gαi2, Gαi3, the Gαi2, protein is predominantly expressed in adipose tissue. However, the functions of the Gαi2 isoform in adipose tissue and its impact on the development of obesity are poorly understood. Methods: By using AdipoqCreERT2 mice, we generated adipocyte-specific Gnai2-deficient mice to study Gαi2 function, specifically in white and brown adipocytes. These mice were fed either a control diet (CD) or a high fat diet (HFD). Mice were examined for obesity development, insulin resistance and glucose intolerance. We examined adipocyte morphology and the development of inflammation in the white adipose tissue. Finally, intracellular cAMP levels as an indicator of Gαi signaling and glycerol release as an indicator of lipolysis rates were measured to verify the impact of Gαi2 on the signaling pathway in brown and white adipocytes. Results: An adipocyte-specific deficiency of Gαi2 significantly reduced diet-induced obesity, leading to decreased fat masses, smaller adipocytes and decreased inflammation in the white adipose tissue relative to littermate controls. Concurrently, oxygen consumption of brown adipocytes and in vivo measured energy expenditure were significantly enhanced. In addition, glucose tolerance and insulin sensitivity of HFD-fed adipocyte-specific Gnai2-deficient mice were improved compared to the respective controls. In the absence of Gαi2, adrenergic stimulation of intracellular adipocyte cAMP levels was increased, which correlated with increased lipolysis and energy expenditure. Conclusion: We conclude that adipocyte Gαi2 is a major regulator of adipocyte lipid content in diet-induced obesity by inhibiting adipocyte lipolysis in a cAMP-dependent manner resulting in increased energy expenditure.
Fil: Leiss, Veronika. Eberhard Karls Universität Tübingen; Alemania
Fil: Schönsiegel, Annika. Eberhard Karls Universität Tübingen; Alemania
Fil: Gnad, Thorsten. Universitat Bonn; Alemania
Fil: Kerner, Johannes. Eberhard Karls Universität Tübingen; Alemania
Fil: Kaur, Jyotsna. Eberhard Karls Universität Tübingen; Alemania
Fil: Sartorius, Tina. Eberhard Karls Universität Tübingen; Alemania
Fil: Machann, Jürgen. Eberhard Karls Universität Tübingen; Alemania
Fil: Schick, Fritz. Eberhard Karls Universität Tübingen; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Häring, Hans Ulrich. Eberhard Karls Universität Tübingen; Alemania
Fil: Pfeifer, Alexander. Universitat Bonn; Alemania
Fil: Nürnberg, Bernd. Eberhard Karls Universität Tübingen; Alemania
description Objectives: Typically, obesity results from an inappropriate balance between energy uptake from nutrient consumption and burning of calories, which leads to a pathological increase in fat mass. Obesity is a major cause of insulin resistance and diabetes. Inhibitory G proteins (Gαi) form a subfamily that is involved in the regulation of adipose tissue function. Among the three Gαi members, i.e. Gαi1, Gαi2, Gαi3, the Gαi2, protein is predominantly expressed in adipose tissue. However, the functions of the Gαi2 isoform in adipose tissue and its impact on the development of obesity are poorly understood. Methods: By using AdipoqCreERT2 mice, we generated adipocyte-specific Gnai2-deficient mice to study Gαi2 function, specifically in white and brown adipocytes. These mice were fed either a control diet (CD) or a high fat diet (HFD). Mice were examined for obesity development, insulin resistance and glucose intolerance. We examined adipocyte morphology and the development of inflammation in the white adipose tissue. Finally, intracellular cAMP levels as an indicator of Gαi signaling and glycerol release as an indicator of lipolysis rates were measured to verify the impact of Gαi2 on the signaling pathway in brown and white adipocytes. Results: An adipocyte-specific deficiency of Gαi2 significantly reduced diet-induced obesity, leading to decreased fat masses, smaller adipocytes and decreased inflammation in the white adipose tissue relative to littermate controls. Concurrently, oxygen consumption of brown adipocytes and in vivo measured energy expenditure were significantly enhanced. In addition, glucose tolerance and insulin sensitivity of HFD-fed adipocyte-specific Gnai2-deficient mice were improved compared to the respective controls. In the absence of Gαi2, adrenergic stimulation of intracellular adipocyte cAMP levels was increased, which correlated with increased lipolysis and energy expenditure. Conclusion: We conclude that adipocyte Gαi2 is a major regulator of adipocyte lipid content in diet-induced obesity by inhibiting adipocyte lipolysis in a cAMP-dependent manner resulting in increased energy expenditure.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
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/11336/140621
Leiss, Veronika; Schönsiegel, Annika; Gnad, Thorsten; Kerner, Johannes; Kaur, Jyotsna; et al.; Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity; Elsevier; Molecular Metabolism; 40; 10-2020; 1-13
2212-8778
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140621
identifier_str_mv Leiss, Veronika; Schönsiegel, Annika; Gnad, Thorsten; Kerner, Johannes; Kaur, Jyotsna; et al.; Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity; Elsevier; Molecular Metabolism; 40; 10-2020; 1-13
2212-8778
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.molmet.2020.101029
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2212877820301034?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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