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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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