Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity

Autores
Michel, Nathaly Anto; Colberg, Christian; Buscher, Konrad; Sommer, Björn; Pramod, Akula Bala; Ehinger, Erik; Dufner, Bianca; Hoppe, Natalie; Pfeiffer, Katharina; Marchini, Timoteo Oscar; Willecke, Florian; Stachon, Peter; Hilgendorf, Ingo; Heidt, Timo; Von Zur Muhlen, Constantin; Von Elverfeldt, Dominik; Pfeifer, Dietmar; Schüle, Roland; Kintscher, Ulrich; Brachs, Sebastian; Ley, Klaus; Bode, Christoph; Zirlik, Andreas; Wolf, Dennis
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rationale: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. Objective: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-a, IL (interleukin)-1ß, and TLRs (toll-like receptors). Methods and Results: Mice defcient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/-mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by ß3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-defcient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Conclusions: Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These fndings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.
Fil: Michel, Nathaly Anto. University of Freiburg. University Medical Center; Alemania
Fil: Colberg, Christian. University of Freiburg. University Medical Center; Alemania
Fil: Buscher, Konrad. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sommer, Björn. Universitat Erlangen-Nuremberg; Alemania
Fil: Pramod, Akula Bala. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ehinger, Erik. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Dufner, Bianca. University of Freiburg. University Medical Center; Alemania
Fil: Hoppe, Natalie. University of Freiburg. University Medical Center; Alemania
Fil: Pfeiffer, Katharina. University of Freiburg. University Medical Center; Alemania
Fil: Marchini, Timoteo Oscar. University of Freiburg. University Medical Center; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Willecke, Florian. University of Freiburg. University Medical Center; Alemania
Fil: Stachon, Peter. University of Freiburg. University Medical Center; Alemania
Fil: Hilgendorf, Ingo. University of Freiburg. University Medical Center; Alemania
Fil: Heidt, Timo. University of Freiburg. University Medical Center; Alemania
Fil: Von Zur Muhlen, Constantin. University of Freiburg. University Medical Center; Alemania
Fil: Von Elverfeldt, Dominik. University of Freiburg. University Medical Center; Alemania
Fil: Pfeifer, Dietmar. University of Freiburg; Alemania
Fil: Schüle, Roland. University of Freiburg; Alemania
Fil: Kintscher, Ulrich. University of Freiburg; Alemania
Fil: Brachs, Sebastian. Center For Cardiovascular Research; Alemania
Fil: Ley, Klaus. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Bode, Christoph. University of Freiburg. University Medical Center; Alemania
Fil: Zirlik, Andreas. University of Freiburg. University Medical Center; Alemania
Fil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados Unidos
Materia
ADIPOCYTES
LIPOLYSIS
METABOLIC SYNDROME
MICE
OBESITY
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:11336/88336
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesityMichel, Nathaly AntoColberg, ChristianBuscher, KonradSommer, BjörnPramod, Akula BalaEhinger, ErikDufner, BiancaHoppe, NataliePfeiffer, KatharinaMarchini, Timoteo OscarWillecke, FlorianStachon, PeterHilgendorf, IngoHeidt, TimoVon Zur Muhlen, ConstantinVon Elverfeldt, DominikPfeifer, DietmarSchüle, RolandKintscher, UlrichBrachs, SebastianLey, KlausBode, ChristophZirlik, AndreasWolf, DennisADIPOCYTESLIPOLYSISMETABOLIC SYNDROMEMICEOBESITYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Rationale: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. Objective: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-a, IL (interleukin)-1ß, and TLRs (toll-like receptors). Methods and Results: Mice defcient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/-mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by ß3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-defcient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Conclusions: Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These fndings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.Fil: Michel, Nathaly Anto. University of Freiburg. University Medical Center; AlemaniaFil: Colberg, Christian. University of Freiburg. University Medical Center; AlemaniaFil: Buscher, Konrad. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sommer, Björn. Universitat Erlangen-Nuremberg; AlemaniaFil: Pramod, Akula Bala. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Ehinger, Erik. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Dufner, Bianca. University of Freiburg. University Medical Center; AlemaniaFil: Hoppe, Natalie. University of Freiburg. University Medical Center; AlemaniaFil: Pfeiffer, Katharina. University of Freiburg. University Medical Center; AlemaniaFil: Marchini, Timoteo Oscar. University of Freiburg. University Medical Center; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Willecke, Florian. University of Freiburg. University Medical Center; AlemaniaFil: Stachon, Peter. University of Freiburg. University Medical Center; AlemaniaFil: Hilgendorf, Ingo. University of Freiburg. University Medical Center; AlemaniaFil: Heidt, Timo. University of Freiburg. University Medical Center; AlemaniaFil: Von Zur Muhlen, Constantin. University of Freiburg. University Medical Center; AlemaniaFil: Von Elverfeldt, Dominik. University of Freiburg. University Medical Center; AlemaniaFil: Pfeifer, Dietmar. University of Freiburg; AlemaniaFil: Schüle, Roland. University of Freiburg; AlemaniaFil: Kintscher, Ulrich. University of Freiburg; AlemaniaFil: Brachs, Sebastian. Center For Cardiovascular Research; AlemaniaFil: Ley, Klaus. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Bode, Christoph. University of Freiburg. University Medical Center; AlemaniaFil: Zirlik, Andreas. University of Freiburg. University Medical Center; AlemaniaFil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados UnidosLippincott Williams2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88336Michel, Nathaly Anto; Colberg, Christian; Buscher, Konrad; Sommer, Björn; Pramod, Akula Bala; et al.; Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity; Lippincott Williams; Circulation Research; 122; 5; 3-2018; 693-7000009-7330CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/CIRCRESAHA.117.312055info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.117.312055info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:36:54Zoai:ri.conicet.gov.ar:11336/88336instacron: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 14:36:54.497CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
title Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
spellingShingle Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
Michel, Nathaly Anto
ADIPOCYTES
LIPOLYSIS
METABOLIC SYNDROME
MICE
OBESITY
title_short Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
title_full Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
title_fullStr Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
title_full_unstemmed Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
title_sort Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity
dc.creator.none.fl_str_mv Michel, Nathaly Anto
Colberg, Christian
Buscher, Konrad
Sommer, Björn
Pramod, Akula Bala
Ehinger, Erik
Dufner, Bianca
Hoppe, Natalie
Pfeiffer, Katharina
Marchini, Timoteo Oscar
Willecke, Florian
Stachon, Peter
Hilgendorf, Ingo
Heidt, Timo
Von Zur Muhlen, Constantin
Von Elverfeldt, Dominik
Pfeifer, Dietmar
Schüle, Roland
Kintscher, Ulrich
Brachs, Sebastian
Ley, Klaus
Bode, Christoph
Zirlik, Andreas
Wolf, Dennis
author Michel, Nathaly Anto
author_facet Michel, Nathaly Anto
Colberg, Christian
Buscher, Konrad
Sommer, Björn
Pramod, Akula Bala
Ehinger, Erik
Dufner, Bianca
Hoppe, Natalie
Pfeiffer, Katharina
Marchini, Timoteo Oscar
Willecke, Florian
Stachon, Peter
Hilgendorf, Ingo
Heidt, Timo
Von Zur Muhlen, Constantin
Von Elverfeldt, Dominik
Pfeifer, Dietmar
Schüle, Roland
Kintscher, Ulrich
Brachs, Sebastian
Ley, Klaus
Bode, Christoph
Zirlik, Andreas
Wolf, Dennis
author_role author
author2 Colberg, Christian
Buscher, Konrad
Sommer, Björn
Pramod, Akula Bala
Ehinger, Erik
Dufner, Bianca
Hoppe, Natalie
Pfeiffer, Katharina
Marchini, Timoteo Oscar
Willecke, Florian
Stachon, Peter
Hilgendorf, Ingo
Heidt, Timo
Von Zur Muhlen, Constantin
Von Elverfeldt, Dominik
Pfeifer, Dietmar
Schüle, Roland
Kintscher, Ulrich
Brachs, Sebastian
Ley, Klaus
Bode, Christoph
Zirlik, Andreas
Wolf, Dennis
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADIPOCYTES
LIPOLYSIS
METABOLIC SYNDROME
MICE
OBESITY
topic ADIPOCYTES
LIPOLYSIS
METABOLIC SYNDROME
MICE
OBESITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Rationale: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. Objective: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-a, IL (interleukin)-1ß, and TLRs (toll-like receptors). Methods and Results: Mice defcient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/-mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by ß3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-defcient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Conclusions: Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These fndings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.
Fil: Michel, Nathaly Anto. University of Freiburg. University Medical Center; Alemania
Fil: Colberg, Christian. University of Freiburg. University Medical Center; Alemania
Fil: Buscher, Konrad. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sommer, Björn. Universitat Erlangen-Nuremberg; Alemania
Fil: Pramod, Akula Bala. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ehinger, Erik. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Dufner, Bianca. University of Freiburg. University Medical Center; Alemania
Fil: Hoppe, Natalie. University of Freiburg. University Medical Center; Alemania
Fil: Pfeiffer, Katharina. University of Freiburg. University Medical Center; Alemania
Fil: Marchini, Timoteo Oscar. University of Freiburg. University Medical Center; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Willecke, Florian. University of Freiburg. University Medical Center; Alemania
Fil: Stachon, Peter. University of Freiburg. University Medical Center; Alemania
Fil: Hilgendorf, Ingo. University of Freiburg. University Medical Center; Alemania
Fil: Heidt, Timo. University of Freiburg. University Medical Center; Alemania
Fil: Von Zur Muhlen, Constantin. University of Freiburg. University Medical Center; Alemania
Fil: Von Elverfeldt, Dominik. University of Freiburg. University Medical Center; Alemania
Fil: Pfeifer, Dietmar. University of Freiburg; Alemania
Fil: Schüle, Roland. University of Freiburg; Alemania
Fil: Kintscher, Ulrich. University of Freiburg; Alemania
Fil: Brachs, Sebastian. Center For Cardiovascular Research; Alemania
Fil: Ley, Klaus. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Bode, Christoph. University of Freiburg. University Medical Center; Alemania
Fil: Zirlik, Andreas. University of Freiburg. University Medical Center; Alemania
Fil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados Unidos
description Rationale: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. Objective: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-a, IL (interleukin)-1ß, and TLRs (toll-like receptors). Methods and Results: Mice defcient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/-mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by ß3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-defcient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Conclusions: Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These fndings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
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/11336/88336
Michel, Nathaly Anto; Colberg, Christian; Buscher, Konrad; Sommer, Björn; Pramod, Akula Bala; et al.; Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity; Lippincott Williams; Circulation Research; 122; 5; 3-2018; 693-700
0009-7330
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88336
identifier_str_mv Michel, Nathaly Anto; Colberg, Christian; Buscher, Konrad; Sommer, Björn; Pramod, Akula Bala; et al.; Inflammatory pathways regulated by tumor necrosis receptor-associated factor 1 protect from metabolic consequences in diet-induced obesity; Lippincott Williams; Circulation Research; 122; 5; 3-2018; 693-700
0009-7330
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1161/CIRCRESAHA.117.312055
info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.117.312055
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 Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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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