CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity
(2017) In Cell Metabolism 26(1). p.6-255- Abstract
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... (More)
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. Jordan et al. show that the circadian transcriptional repressors CRY1 and CRY2 repress the nuclear hormone receptor PPARδ and its target genes in mouse skeletal muscle and modulate exercise performance by altering substrate selectivity for energy production.
(Less)
- author
- organization
- publishing date
- 2017-07-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- beta oxidation, circadian, clock, CRY1, CRY2, cryptochrome, exercise, muscle, PPAR, sprint
- in
- Cell Metabolism
- volume
- 26
- issue
- 1
- pages
- 6 - 255
- publisher
- Cell Press
- external identifiers
-
- scopus:85027411247
- pmid:28683290
- ISSN
- 1550-4131
- DOI
- 10.1016/j.cmet.2017.06.002
- language
- English
- LU publication?
- no
- id
- 17024bda-6954-4b5f-9338-f9117aecc106
- date added to LUP
- 2018-01-25 12:35:55
- date last changed
- 2024-03-31 22:36:44
@article{17024bda-6954-4b5f-9338-f9117aecc106, abstract = {{<p>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<sup>−/−</sup>;Cry2<sup>−/−</sup> 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. Jordan et al. show that the circadian transcriptional repressors CRY1 and CRY2 repress the nuclear hormone receptor PPARδ and its target genes in mouse skeletal muscle and modulate exercise performance by altering substrate selectivity for energy production.</p>}}, author = {{Jordan, Sabine D. and Kriebs, Anna and Vaughan, Megan and Duglan, Drew and Fan, Weiwei and Henriksson, Emma and Huber, Anne Laure and Papp, Stephanie J. and Nguyen, Madelena and Afetian, Megan and Downes, Michael and Yu, Ruth T. and Kralli, Anastasia and Evans, Ronald M. and Lamia, Katja A.}}, issn = {{1550-4131}}, keywords = {{beta oxidation; circadian; clock; CRY1; CRY2; cryptochrome; exercise; muscle; PPAR; sprint}}, language = {{eng}}, month = {{07}}, number = {{1}}, pages = {{6--255}}, publisher = {{Cell Press}}, series = {{Cell Metabolism}}, title = {{CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity}}, url = {{http://dx.doi.org/10.1016/j.cmet.2017.06.002}}, doi = {{10.1016/j.cmet.2017.06.002}}, volume = {{26}}, year = {{2017}}, }