ArticleCell metabolism2016
AMPK/α-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis.
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 149 papers.
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Who cites it
149 citing papers in PubMed, 232 citations in OpenAlex.
- The Ageing Adipose Paradox: Implications for Metabolic Health.Diabetes, obesity & metabolism · 2026Review
- H19 lncRNA in programming prenatal development and DOHaD due to maternal obesity.Life sciences · 2026Review
- Exclusive Breastfeeding Drives AMPK-Dependent Thermogenic Memory in BAT and Promotes Long-Term Metabolic Benefits in Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immune-epigenetic-metabolic crosstalk: attempting to unravel the multidimensional mechanisms of immune evasion in endometriosis.Frontiers in immunology · 2026Review
- AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.Molecular nutrition & food research · 2025Article
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming.Cell death discovery · 2025Article
- Obesity: pathophysiology and therapeutic interventions.Molecular biomedicine · 2025Review
- Cross-talks between Metabolic and Translational Controls during Beige Adipocyte Differentiation.Nature communications · 2025Article
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- Correlation between α-ketoglutarate and the oxidative stress response in patients with coronary heart disease and prognostic analysis of interventional therapy for coronary heart disease.Frontiers in cardiovascular medicine · 2025Article
- Alpha-ketoglutarate supplementation improves hyperglycemia and attenuates the decrease in GLUT4 and PGC-1α proteins in adipose tissue of streptozotocin-high-fat diet-induced diabetic mice.Journal of nutritional science · 2025Article
- WTAP Maintains Alternative Activation of Macrophages by Promoting IDH1-Mediated α-ketoglutarate Production.International journal of biological sciences · 2025Article
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- Single-cell RNA transcriptomics in mice reveals embryonic origin of fibrosis due to maternal obesity.EBioMedicine · 2024Article
- Hederagenin fromPlants (Basel, Switzerland) · 2024Article
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- Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.Cardiovascular diabetology · 2024Article
- Alpha-Lipoic Acid Induces Adipose Tissue Browning through AMP-Activated Protein Kinase SignalingJournal of obesity & metabolic syndrome · 2024Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Promoting brown adipose tissue (BAT) development is an attractive strategy for the treatment of obesity, as activated BAT dissipates energy through thermogenesis; however, the mechanisms controlling BAT formation are not fully understood. We hypothesized that as a master regulator of energy metabolism, AMP-activated protein kinase (AMPK) may play a direct role in the process and found that AMPKα1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of α-ketoglutarate (αKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter. AMPKα1 ablation reduced isocitrate dehydrogenase 2 activity and cellular αKG levels. Remarkably, postnatal AMPK activation with AICAR or metformin rescued obesity-induced suppression of brown adipogenesis and thermogenesis. In summary, AMPK is essential for the epigenetic control of BAT development through αKG, thus linking a metabolite to progenitor cell differentiation and thermogenesis.
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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.