Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/153809
Title: GDF15 mediates the metabolic effects of PPARβ/δ by activating AMPK
Authors: Aguilar-Recarte, David
Barroso, Emma
Gumà, Anna
Pizarro-Delgado, Javier
Peña, Lucía
Ruart, Maria
Palomer, Xavier
Wahli, Walter
Vázquez-Carrera, Manuel
Keywords: Science::Medicine
Issue Date: 2021
Source: Aguilar-Recarte, D., Barroso, E., Gumà, A., Pizarro-Delgado, J., Peña, L., Ruart, M., Palomer, X., Wahli, W. & Vázquez-Carrera, M. (2021). GDF15 mediates the metabolic effects of PPARβ/δ by activating AMPK. Cell Reports, 36(6), 109501-. https://dx.doi.org/10.1016/j.celrep.2021.109501
Journal: Cell Reports
Abstract: Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examine whether PPARβ/δ activation effects depend on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARβ/δ 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 PPARβ/δ-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 PPARβ/δ activation increases GDF15 levels via AMPK and p53, which in turn mediates the metabolic effects of PPARβ/δ by sustaining AMPK activation.
URI: https://hdl.handle.net/10356/153809
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.109501
Rights: © 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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