Highlights d Activation of the AMPK-p53 pathway by PPARb/d agonists increases GDF15 d Many metabolic effects mediated by PPARb/d activation are abrogated in Gdf15 À/À mice d GDF15 is required for the activation of AMPK by ligandactivated PPARb/d d In skeletal muscle, GDF15 activates AMPK in the absence of the GDF15 receptor GFRAL
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