The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.
The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome
Open accessAbstract
SUMMARY Dysregulation of circadian rhythms is associated with metabolic dysfunction, yet it is unclear whether enhancing clock function can ameliorate metabolic disorders. In an unbiased chemical screen using fibroblasts expressing PER2::Luc, we identified Nobiletin (NOB), a natural polymethoxylated flavone, as a Clock amplitude-Enhancing small Molecule (CEM). When administered to diet-induced obese (DIO) mice, NOB strongly counteracted metabolic syndrome and augmented energy expenditure and locomotor activity in a Clock gene-dependent manner. In db/db mutant mice, the clock is also required for the mitigating effects of NOB on metabolic disorders. In DIO mouse liver, NOB enhanced clock protein levels and elicited pronounced gene expression remodeling. We identified retinoid acid receptor-related orphan receptors (RORs) as direct targets of NOB, revealing a pharmacological intervention that enhances circadian rhythms to combat metabolic disease via the circadian gene network.
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Self-citationHigh-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice
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Cited by
Molecular mechanisms and physiological importance of circadian rhythms
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Circadian rhythm as a therapeutic target
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Metadata
- Authors
- He, B., Nohara, K., Park, N., Park, Y.-S., Guillory, B., Zhao, Z., Garcia, J. M., Koike, N., Lee, C. C., Takahashi, J. S., Yoo, S.-H., & Chen, Z.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 23
- Issue
- 4
- Pages
- 610-621
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2342036008
- Cited by
- 507
- References
- 86
- FWCI
- 20.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- He, B., Nohara, K., Park, N., Park, Y.-S., Guillory, B., Zhao, Z., Garcia, J. M., Koike, N., Lee, C. C., Takahashi, J. S., Yoo, S.-H., & Chen, Z. (2016). The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome. Cell Metabolism. https://doi.org/10.1016/j.cmet.2016.03.007
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