mouse C2C12 cells ChIP-Seq of PPARdelta. Mus musculus

We show that exercise mimetics targeting PPARδ promote endurance, increasing running time in sedentary mice without affecting muscle fiber type or mitochondrial content. Unexpectedly, PPARδ activation not only promotes fatty acid metabolism but coordinately suppresses glycolytic genes in muscle. This PPARδ-dependent binary substrate shift preserves glucose by preferentially burning fat, delaying the onset of hypoglycemia during endurance exercise by ~100 minutes in treated mice.