GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.

Peroxisome proliferator-activated receptor ß/d (PPARß/d) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examine whether PPARß/d activation effects depend on growth differentiation factor 15 (GDF15), a stress response cytokine that reg...

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Autores: Aguilar-Recarte D, Barroso E, Gumà A, Pizarro-Delgado J, Peña L, Ruart M, Palomer X, Wahli W, Vázquez-Carrera M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p19957
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19957
Access Level:acceso abierto
Palabra clave:*AMPK
*GDF15
*PPARß/d
*glucose tolerance
*p53
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spelling GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.Aguilar-Recarte DBarroso EGumà APizarro-Delgado JPeña LRuart MPalomer XWahli WVázquez-Carrera M*AMPK*GDF15*PPARß/d*glucose tolerance*p53Peroxisome proliferator-activated receptor ß/d (PPARß/d) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examine whether PPARß/d activation effects depend on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARß/d activation increases GDF15 levels and ameliorates glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, and inflammation, and activates AMPK in HFD-fed mice, whereas these effects are abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15(-/-) mice. The AMPK-p53 pathway is involved in the PPARß/d-mediated increase in GDF15, which in turn activates again AMPK. Consistently, Gdf15(-/-) mice show reduced AMPK activation in skeletal muscle, whereas GDF15 administration results in AMPK activation in this organ. Collectively, these data reveal a mechanism by which PPARß/d activation increases GDF15 levels via AMPK and p53, which in turn mediates the metabolic effects of PPARß/d by sustaining AMPK activation.CELL PRESS2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19957Cell ReportsISSN: 26391856ISSNe: 22111247reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p199572026-05-27T12:37:41Z
dc.title.none.fl_str_mv GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
title GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
spellingShingle GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
Aguilar-Recarte D
*AMPK
*GDF15
*PPARß/d
*glucose tolerance
*p53
title_short GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
title_full GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
title_fullStr GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
title_full_unstemmed GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
title_sort GDF15 mediates the metabolic effects of PPARß/d by activating AMPK.
dc.creator.none.fl_str_mv Aguilar-Recarte D
Barroso E
Gumà A
Pizarro-Delgado J
Peña L
Ruart M
Palomer X
Wahli W
Vázquez-Carrera M
author Aguilar-Recarte D
author_facet Aguilar-Recarte D
Barroso E
Gumà A
Pizarro-Delgado J
Peña L
Ruart M
Palomer X
Wahli W
Vázquez-Carrera M
author_role author
author2 Barroso E
Gumà A
Pizarro-Delgado J
Peña L
Ruart M
Palomer X
Wahli W
Vázquez-Carrera M
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv *AMPK
*GDF15
*PPARß/d
*glucose tolerance
*p53
topic *AMPK
*GDF15
*PPARß/d
*glucose tolerance
*p53
description Peroxisome proliferator-activated receptor ß/d (PPARß/d) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examine whether PPARß/d activation effects depend on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARß/d activation increases GDF15 levels and ameliorates glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, and inflammation, and activates AMPK in HFD-fed mice, whereas these effects are abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15(-/-) mice. The AMPK-p53 pathway is involved in the PPARß/d-mediated increase in GDF15, which in turn activates again AMPK. Consistently, Gdf15(-/-) mice show reduced AMPK activation in skeletal muscle, whereas GDF15 administration results in AMPK activation in this organ. Collectively, these data reveal a mechanism by which PPARß/d activation increases GDF15 levels via AMPK and p53, which in turn mediates the metabolic effects of PPARß/d by sustaining AMPK activation.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19957
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19957
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv CELL PRESS
publisher.none.fl_str_mv CELL PRESS
dc.source.none.fl_str_mv Cell Reports
ISSN: 26391856
ISSNe: 22111247
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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