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The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect Against Metabolic Syndrome

The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect Against Metabolic Syndrome

Baokun He, Kazunari Nohara, Noheon Park, Yong-Sung Park, Bobby Guillory, Zhaoyang Zhao, Jose M Garcia, Nobuya Koike, Cheng Chi Lee, Joseph S Takahashi, Seung-Hee Yoo, Zheng Chen

Cell Metab. 2016 Apr 12;23(4):610-21.

PMID: 27076076

Abstract:

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. 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 as direct targets of NOB, revealing a pharmacological intervention that enhances circadian rhythms to combat metabolic disease via the circadian gene network.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
CS3102542	Nobiletin			Price

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