CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity
| Autor: | Anne Laure Huber, Drew Duglan, Katja A. Lamia, Anastasia Kralli, Megan E. Afetian, Megan Vaughan, Ronald M. Evans, Michael Downes, Weiwei Fan, Sabine D. Jordan, Stephanie J. Papp, Ruth T. Yu, Madelena Nguyen, Emma Henriksson, Anna Kriebs |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty endocrine system animal structures Physiology Peroxisome proliferator-activated receptor Context (language use) Biology Article 03 medical and health sciences Mice 0302 clinical medicine Cryptochrome Internal medicine Physical Conditioning Animal medicine Animals Circadian rhythm PPAR delta Protein Interaction Maps Receptor Molecular Biology Transcription factor Nuclear receptor co-repressor 1 Cells Cultured chemistry.chemical_classification Mice Knockout Myogenesis Muscles Cell Biology Cryptochromes Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Gene Expression Regulation sense organs 030217 neurology & neurosurgery Gene Deletion |
| Zdroj: | Cell metabolism. 26(1) |
| ISSN: | 1932-7420 |
| Popis: | Summary 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 (PPARδ) 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 PPARδ. Cry1 −/− ; Cry2 −/− myotubes and muscles exhibit elevated expression of PPARδ target genes, particularly in the context of exercise. Notably, CRY1/2 seem to repress a distinct subset of PPARδ 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 PPARδ, and thereby alter energy storage and substrate selection for energy production. |
| Databáze: | OpenAIRE |
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