1. PPARδ Promotes Running Endurance by Preserving Glucose
- Author
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Chun Shi Lin, Annette R. Atkins, Weiwei Fan, Christopher Liddle, Wanda Waizenegger, Christopher E. Wall, Ronald M. Evans, Michael Downes, Johan Auwerx, Vincenzo Sorrentino, Ruth T. Yu, Mingxiao He, and Hao Li
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Physiology ,Hypoglycemia ,Biology ,Carbohydrate metabolism ,Article ,Cell Line ,Running ,Myoblasts ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Endurance training ,Internal medicine ,Physical Conditioning, Animal ,medicine ,Myocyte ,Animals ,PPAR delta ,Metabolic disease ,Muscle, Skeletal ,Molecular Biology ,Fatty acid metabolism ,Fatty Acids ,Cell Biology ,medicine.disease ,Running time ,Mitochondria, Muscle ,030104 developmental biology ,Endocrinology ,Glucose ,chemistry ,Physical Endurance ,Peroxisome proliferator-activated receptor delta - Abstract
Management of energy stores is critical during endurance exercise, with a shift in substrate utilization from glucose towards fat being a hallmark of trained muscle. Here we show that this key metabolic adaptation is both dependent on muscle PPARδ and stimulated by PPARδ ligand. Furthermore, we find that muscle PPARδ expression positively correlates with endurance performance in BXD mouse reference populations. In addition to stimulating fatty acid metabolism in sedentary mice, PPARδ activation potently suppresses glucose catabolism and does so without affecting either muscle fiber type or mitochondrial content. By preserving systemic glucose levels PPARδ acts to delay the onset of hypoglycemia and extends running time by ~100 minutes in treated mice. Collectively, these results identify a bifurcated PPARδ program that underlies glucose sparing and highlight the potential of PPARδ-targeted exercise mimetics in the treatment of metabolic disease, dystrophies and unavoidably, the enhancement of athletic performance.
- Published
- 2016