Related Experiment Video
Updated: Feb 27, 2026
07:52
Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise
Published on: August 14, 2014
20.1K
CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity.
Sabine D Jordan1, Anna Kriebs2, Megan Vaughan2
1Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Metabolism
|July 7, 2017
Summary
The circadian repressors CRY1 and CRY2 act as co-repressors for PPARδ, influencing lipid metabolism and exercise endurance. Disrupting CRY1 and CRY2 enhances sprint performance by altering energy substrate selection.
Area of Science:
- Circadian Biology
- Metabolic Regulation
- Exercise Physiology
Background:
- Cellular metabolism and mitochondrial function are influenced by circadian rhythms, but the underlying molecular mechanisms remain largely unknown.
- Peroxisome proliferator-activated receptor delta (PPARδ) is crucial for lipid utilization during exercise and enhances endurance.
- The precise connections between the molecular clock and metabolic pathways controlling energy homeostasis are not fully elucidated.
Purpose of the Study:
- To investigate the role of circadian repressors CRY1 and CRY2 in regulating PPARδ activity and its downstream effects on cellular metabolism and exercise performance.
- To determine if CRY1 and CRY2 function as co-repressors for PPARδ and influence its target gene expression.
- To elucidate the impact of CRY1/2 disruption on exercise physiology and energy substrate utilization.
Main Methods:
- Utilized myotubes and muscle tissues from Cry1-/-;Cry2-/- mice to assess gene expression patterns.
- Performed in vivo studies in mice with genetic disruption of Cry1 and Cry2 to evaluate sprint exercise performance.
- Analyzed the co-repression activity of CRY1/2 on PPARδ target genes in comparison to known co-repressors like NCOR1.
Main Results:
- Demonstrated that CRY1 and CRY2 function as co-repressors for PPARδ.
- Observed elevated expression of PPARδ target genes in Cry1-/-;Cry2-/- myotubes and muscles, especially during exercise.
- Showcased that CRY1/2 repress a distinct set of PPARδ target genes in muscle compared to NCOR1.
- Confirmed that genetic disruption of Cry1 and Cry2 significantly enhances sprint exercise performance in mice.
Conclusions:
- CRY1 and CRY2 play a significant role in modulating exercise physiology.
- These circadian repressors alter the activity of transcription factors, including CLOCK/BMAL1 and PPARδ.
- CRY1/2 influence energy storage and the selection of substrates for energy production, impacting overall exercise capacity.
Related Concept Videos
01:31Transducer Mechanism: Nuclear Receptors
3.6K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
3.6K
01:58Cell Specific Gene Expression
16.7K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.7K
01:09GPCRs Regulate Adenylyl Cylase Activity
7.8K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.8K
02:23Master Transcription Regulators
7.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K
01:25cAMP-dependent Protein Kinase Pathways
8.7K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.7K
02:04Co-activators and Co-repressors
8.7K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.7K