mouse C2C12 cells ChIP-Seq of PPARdelta

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