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http://hdl.handle.net/2445/180474
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DC Field | Value | Language |
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dc.contributor.author | Aguilar-Recarte, David | - |
dc.contributor.author | Barroso Fernández, Emma | - |
dc.contributor.author | Gumà i Garcia, Anna Maria | - |
dc.contributor.author | Pizarro Delgado, Javier | - |
dc.contributor.author | Peña, Lucía | - |
dc.contributor.author | Ruart, Maria | - |
dc.contributor.author | Palomer Tarridas, Francesc Xavier | - |
dc.contributor.author | Wahli, Walter | - |
dc.contributor.author | Vázquez Carrera, Manuel | - |
dc.date.accessioned | 2021-10-07T09:22:36Z | - |
dc.date.available | 2021-10-07T09:22:36Z | - |
dc.date.issued | 2021-07-16 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | http://hdl.handle.net/2445/180474 | - |
dc.description.abstract | Peroxisome proliferator-activated receptor β/ (PPARβ/) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examined whether the beneficial effects of PPARβ/δ activation depended on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARβ/δ activation increased GDF15 levels and ameliorated glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, inflammation and activated AMPK in HFD-fed mice, whereas these effects were abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15-/- mice. The AMPK-p53 pathway was involved in the PPARβ/δ-mediated increase in GDF15, which in turn activated again AMPK. Finally, Gdf15-/- mice showed reduced AMPK activation in skeletal muscle, whereas GDF15 administration resulted in AMPK activation in this organ. Collectively, these data reveal a novel mechanism by which PPARβ/δ activation increases the levels of GDF15 via AMPK and p53, which in turn mediates the metabolic effects of PPARβ/δ by sustaining AMPK activation. Abbreviations: Acadm, acyl-CoA dehydrogenase medium chain; Acox, acyl-CoA oxidase; AMPK, AMP-activated protein kinase; ATF4, activating transcription factor 4; BiP/GRP78, Binding immunoglobulin protein/78-kDa glucose-regulated protein; CC, compound C; Chop, C/EBP homologous protein; Cpt-1, carnitine palmitoyl-transferase 1; eIF2eukaryotic translation initiation factor 2 ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; FGF21, fibroblast growth factor 21; GDF15, growth differentiation factor 15; GFRAL, glial-derived neurotrophic factor receptor α-like; HFD, high-fat diet; Pdk4, pyruvate dehydrogenase kinase 4; IRS, insulin receptor substrate; PGC-1PPAR co-activator 1 PPAR peroxisome proliferator-activated receptor; SOCS3, suppressor of cytokine signaling 3; STAT3, signal transducer and activator of transcription 3; Vldlr, very-low density lipoprotein receptor. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2021.109501 | - |
dc.relation.ispartof | Cell Reports, 2021, vol. 36, num. 6, p. 109501 | - |
dc.relation.uri | https://doi.org/10.1016/j.celrep.2021.109501 | - |
dc.rights | cc-by (c) Aguilar-Recarte, David et al., 2021 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Trastorns del metabolisme dels lípids | - |
dc.subject.classification | Àcids grassos | - |
dc.subject.classification | Receptors nuclears (Bioquímica) | - |
dc.subject.classification | Glucosa | - |
dc.subject.other | Lipid metabolism disorders | - |
dc.subject.other | Fatty acids | - |
dc.subject.other | Nuclear receptors (Biochemistry) | - |
dc.subject.other | Glucose | - |
dc.title | GDF15 mediates the metabolic effects of PPARβ/δ by activating AMPK | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 713345 | - |
dc.date.updated | 2021-10-07T09:22:36Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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