ArticleCell metabolism2016
The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome.
Article in Cell metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 285 papers.
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Who cites it
285 citing papers in PubMed, 486 citations in OpenAlex.
- Circadian mechanisms in heart failure: Cell-specific regulation and chrono-medicine.Cell insight · 2026Review
- BMAL1 in cardiovascular diseases: Molecular mechanisms, circadian regulation and translational perspectives (Review).Molecular medicine reports · 2026Review
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- REV-ERB-Mediated Regulation of Neural Functional Mechanisms by Phytochemicals in the Circadian System.Nutrients · 2026Review
- Hesperetin Attenuates Experimentally Induced Skeletal Muscle Dysfunction by Modulating Time-of-Day-Dependent Gene Expression and Mitochondrial Redox-Related Markers.Antioxidants (Basel, Switzerland) · 2026Article
- Nobiletin as a Geroprotective Flavonoid: Mechanisms of Action, Therapeutic Potential, and Challenges of Bioavailability.Antioxidants (Basel, Switzerland) · 2026Review
- Discovery of circadian clock activators with anti-obesity efficacy via suppression of adipocyte development and hypertrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The nuclear receptor ROR-alpha is a putative novel myogenic regulator of the cardiomyocyte transcriptome, including the alpha-1A adrenergic receptor.American journal of physiology. Heart and circulatory physiology · 2026Article
- Circadian clock and its potential as a therapy for ischemic heart disease.Cell communication and signaling : CCS · 2026Review
- Circadian Regulation of Glucose Metabolism: Implications for Pathogenesis and Chronotherapy of Type 2 Diabetes.Diabetology · 2026Article
- Perturbation of the circadian rhythmic transcription contributes to radiotherapy-induced salivary gland hypofunction.Communications biology · 2026Article
- Identification of circadian rhythm-associated key genes in metabolic dysfunction-associated fatty liver disease.Clinical and experimental medicine · 2026Article
- Association Between the Meal Timing of Dietary Flavonoids and Non-Alcoholic Fatty Liver Disease in U.S. Adults: An NHANES Analysis.Healthcare (Basel, Switzerland) · 2026Article
- Cryptochrome Loss Drives COPD-like Lung Pathology through Disrupted Alveolar Epithelial Proliferation and Immune Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Quercetin and Fisetin activate circadian clock via RORα and inhibit adipocyte growth.bioRxiv : the preprint server for biology · 2026Article
- Noncanonical clock regulators control stress responses in digestive diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Impact of acute blue light irradiation on the molecular clock and markers associated with photoaging in skin cell models.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Clock Modulation by Naringenin Suppresses Lipogenesis and Promotes Adipose Tissue Browning.Journal of cellular physiology · 2026Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
225 more citing papers are in PubMed but not listed here.
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12 authors at 4 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.