ArticleThe Journal of clinical investigation2022
TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Obesity Disrupts CtBP2-Mediated Maintenance of Transcriptional Equilibrium in Hypothalamic Feeding Circuitry.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Comprehensive insights into emerging advances in the Neurobiology of anorexia.Journal of advanced research · 2026Review
- MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Genetics of Anorexia Nervosa: Translation to Future Personalized Therapies.The Psychiatric clinics of North America · 2025Review
- Dopaminergic neurons in the paraventricular hypothalamus extend the food consumption phase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The De Ritis ratio mediates the association between creatinine-to-body weight ratio and normoglycemic conversion in Chinese health examinees.Scientific reports · 2025Article
- Review
- DNA methylation and demethylation in adipocyte biology: roles of DNMT and TET proteins in metabolic disorders.Frontiers in endocrinology · 2025Review
- TET3-overexpressing macrophages promote endometriosis.The Journal of clinical investigation · 2024Article
- Targeting TET3 in macrophages provides a concept strategy for the treatment of endometriosis.The Journal of clinical investigation · 2024Article
- Article
- Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α.Diabetologia · 2024Article
- Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice.Physiological genomics · 2024Article
- DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development.The Journal of biological chemistry · 2024Article
- DNA Methylation in the Hypothalamic Feeding Center and Obesity.Journal of obesity & metabolic syndrome · 2023Review
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Programming of metabolism by adipokines during development.Nature reviews. Endocrinology · 2023Review
- Neuropeptide Y Peptide Family and Cancer: Antitumor Therapeutic Strategies.International journal of molecular sciences · 2023Review
- A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.
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Registered trials
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