First Author | Fan W | Year | 2017 |
Journal | Cell Metab | Volume | 25 |
Issue | 5 | Pages | 1186-1193.e4 |
PubMed ID | 28467934 | Mgi Jnum | J:256742 |
Mgi Id | MGI:6106800 | Doi | 10.1016/j.cmet.2017.04.006 |
Citation | Fan W, et al. (2017) PPARdelta Promotes Running Endurance by Preserving Glucose. Cell Metab 25(5):1186-1193.e4 |
abstractText | Management of energy stores is critical during endurance exercise; a shift in substrate utilization from glucose toward fat is a hallmark of trained muscle. Here we show that this key metabolic adaptation is both dependent on muscle PPARdelta and stimulated by PPARdelta ligand. Furthermore, we find that muscle PPARdelta expression positively correlates with endurance performance in BXD mouse reference populations. In addition to stimulating fatty acid metabolism in sedentary mice, PPARdelta activation potently suppresses glucose catabolism and does so without affecting either muscle fiber type or mitochondrial content. By preserving systemic glucose levels, PPARdelta acts to delay the onset of hypoglycemia and extends running time by approximately 100 min in treated mice. Collectively, these results identify a bifurcated PPARdelta program that underlies glucose sparing and highlight the potential of PPARdelta-targeted exercise mimetics in the treatment of metabolic disease, dystrophies, and, unavoidably, the enhancement of athletic performance. |