ArticleJCI insight2018
Cyclin-dependent kinase 4 is a preclinical target for diet-induced obesity.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The Impact of Obesity on Treatment Outcomes in Patients with Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Receiving CDK 4/6 Inhibitors.Cancer research and treatment · 2026Pooled it
- Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy.Journal of the National Cancer Institute · 2021Trial
- Association Between Body Mass Index and Clinical Outcomes of CDK4/6 Inhibitors in HR+/HER2- Metastatic Breast Cancer: A Real-World Cohort Study.Journal of clinical medicine · 2026Article
- Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- The correlation between obesity and the occurrence and development of breast cancer.European journal of medical research · 2025Review
- Steatotic liver disease in metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor.Breast cancer research and treatment · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Diet-induced Obesity: Pathophysiology, Consequences and Target Specific Therapeutic Strategies.Current protein & peptide science · 2025Review
- Visceral obesity and sarcopenia as predictors of efficacy and hematological toxicity in patients with metastatic breast cancer treated with CDK 4/6 inhibitors.Cancer chemotherapy and pharmacology · 2024Article
- CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver.Nature communications · 2024Article
- Prenatal benzene exposure in mice alters offspring hypothalamic development predisposing to metabolic disease in later life.Chemosphere · 2023Article
- Evaluation of the relationship between toxicity of cyclin-dependent kinase 4/6 inhibitors and body surface area.Revista da Associacao Medica Brasileira (1992) · 2023Article
- Review
- Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Do body composition parameters correlate with response to targeted therapy in ER+/HER2- metastatic breast cancer patients? Role of sarcopenia and obesity.Frontiers in oncology · 2022Article
- Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.International journal of molecular sciences · 2021Review
- Cyclin-dependent kinase 4/6 inhibitors require an arcuate-to-paraventricular hypothalamus melanocortin circuit to treat diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2021Article
- Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.EMBO reports · 2020Article
- Neuronal Cell Cycle Events Link Caloric Intake to Obesity.Trends in endocrinology and metabolism: TEM · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
When obesity is caused by consumption of a high-fat diet, the tumor suppressor pRb is phosphoinactivated in the neurons of the mediobasal hypothalamus, a brain area critical for energy-balance regulation. However, the functional relevance of pRb phosphoinactivation in the mediobasal hypothalamus to diet-induced obesity remains unknown. Here, we show that inhibiting pRb phosphorylation in the mediobasal hypothalamus can prevent and treat diet-induced obesity in mice. Expressing an unphosphorylable pRb nonselectively in the mediobasal hypothalamus or conditionally in anorexigenic POMC neurons inhibits diet-induced obesity. Intracerebroventricular delivery of US Food and Drug Administration-approved (FDA-approved) cyclin-dependent kinase 4 (CDK4) inhibitor abemaciclib inhibits pRb phosphorylation in the mediobasal hypothalamus and prevents diet-induced obesity. Oral administration of abemaciclib at doses approved for human use reduces fat mass in diet-induced obese mice by increasing lipid oxidation without significantly reducing lean mass. With analysis of recent literature identifying CDK4 as the most abundantly expressed neuronal CDK in the mediobasal hypothalamus, our work uncovers CDK4 as the major kinase for hypothalamic pRb phosphoinactivation and a highly effective central antiobesity target. As three CDK4/6 inhibitors have recently received FDA approval for life-long breast cancer therapy, our study provides a preclinical basis for their expedient repurposing for obesity management.
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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.