| First Author | Aguilar-Recarte D | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 6 | Pages | 109501 |
| PubMed ID | 34380027 | Mgi Jnum | J:311478 |
| Mgi Id | MGI:6765699 | Doi | 10.1016/j.celrep.2021.109501 |
| Citation | Aguilar-Recarte D, et al. (2021) GDF15 mediates the metabolic effects of PPARbeta/delta by activating AMPK. Cell Rep 36(6):109501 |
| abstractText | Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examine whether PPARbeta/delta activation effects depend on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARbeta/delta 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 PPARbeta/delta-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 PPARbeta/delta activation increases GDF15 levels via AMPK and p53, which in turn mediates the metabolic effects of PPARbeta/delta by sustaining AMPK activation. |
