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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/140621
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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 Técnicas2025-09-29T10:37:38Zoai: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:34982025-09-29 10:37:39.109CONICET 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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13.070432 |