GDF15 mediates the metabolic effects of PPARβ/δ by activating AMPK.

Details

Serval ID
serval:BIB_66044934741B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
GDF15 mediates the metabolic effects of PPARβ/δ by activating AMPK.
Journal
Cell reports
Author(s)
Aguilar-Recarte D., Barroso E., Gumà A., Pizarro-Delgado J., Peña L., Ruart M., Palomer X., Wahli W., Vázquez-Carrera M.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
10/08/2021
Peer-reviewed
Oui
Volume
36
Number
6
Pages
109501
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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 <sup>-/-</sup> mice. The AMPK-p53 pathway is involved in the PPARβ/δ-mediated increase in GDF15, which in turn activates again AMPK. Consistently, Gdf15 <sup>-/-</sup> 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.
Keywords
AMPK, GDF15, PPARβ/δ, glucose tolerance, p53
Pubmed
Web of science
Open Access
Yes
Create date
24/08/2021 12:23
Last modification date
04/09/2021 5:34
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