| First Author | Jordan SD | Year | 2017 |
| Journal | Cell Metab | Volume | 26 |
| Issue | 1 | Pages | 243-255.e6 |
| PubMed ID | 28683290 | Mgi Jnum | J:255965 |
| Mgi Id | MGI:6107163 | Doi | 10.1016/j.cmet.2017.06.002 |
| Citation | Jordan SD, et al. (2017) CRY1/2 Selectively Repress PPARdelta and Limit Exercise Capacity. Cell Metab 26(1):243-255.e6 |
| abstractText | Cellular metabolite balance and mitochondrial function are under circadian control, but the pathways connecting the molecular clock to these functions are unclear. Peroxisome proliferator-activated receptor delta (PPARdelta) enables preferential utilization of lipids as fuel during exercise and is a major driver of exercise endurance. We show here that the circadian repressors CRY1 and CRY2 function as co-repressors for PPARdelta. Cry1(-/-);Cry2(-/-) myotubes and muscles exhibit elevated expression of PPARdelta target genes, particularly in the context of exercise. Notably, CRY1/2 seem to repress a distinct subset of PPARdelta target genes in muscle compared to the co-repressor NCOR1. In vivo, genetic disruption of Cry1 and Cry2 enhances sprint exercise performance in mice. Collectively, our data demonstrate that CRY1 and CRY2 modulate exercise physiology by altering the activity of several transcription factors, including CLOCK/BMAL1 and PPARdelta, and thereby alter energy storage and substrate selection for energy production. |
