ArticleAging cell2020
Dietary alpha-ketoglutarate promotes beige adipogenesis and prevents obesity in middle-aged mice.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 108 citations in OpenAlex.
- Article
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- From Lipids to Mitochondria: Shared Metabolic Alterations in Obesity and Alzheimer's Disease.Cells · 2026Review
- Article
- α-Ketoglutarate promotes amino acid depletion and suppresses B-cell lymphoma growth and development.Blood · 2025Article
- Bifidobacterium animalis subsp. Lactis BX-BC08 modulates gut microbiota and secretes alpha-Ketoglutaric acid to alleviate MC903-induced atopic dermatitis.Journal of translational medicine · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Identification of 1,400 metabolites as mediators of obesity in 473 gut microbiota taxa: a mediation Mendelian randomization study.Microbiology spectrum · 2025Article
- Cross-talks between Metabolic and Translational Controls during Beige Adipocyte Differentiation.Nature communications · 2025Article
- Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression.Biomolecules · 2025Review
- Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.Acta biochimica et biophysica Sinica · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Serine metabolism in aging and age-related diseases.GeroScience · 2025Review
- Mechanisms of metabolic reprogramming in abdominal aortic aneurysm.Frontiers in cell and developmental biology · 2025Review
- Article
- WTAP Maintains Alternative Activation of Macrophages by Promoting IDH1-Mediated α-ketoglutarate Production.International journal of biological sciences · 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
- Amelioration of aging-induced muscular decline by black soybean (Frontiers in immunology · 2025Article
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Alpha-ketoglutarate ameliorates age-related and surgery induced temporomandibular joint osteoarthritis via regulating IKK/NF-κB signaling.Aging cell · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Aging usually involves the progressive development of certain illnesses, including diabetes and obesity. Due to incapacity to form new white adipocytes, adipose expansion in aged mice primarily depends on adipocyte hypertrophy, which induces metabolic dysfunction. On the other hand, brown adipose tissue burns fatty acids, preventing ectopic lipid accumulation and metabolic diseases. However, the capacity of brown/beige adipogenesis declines inevitably during the aging process. Previously, we reported that DNA demethylation in the Prdm16 promoter is required for beige adipogenesis. DNA methylation is mediated by ten-eleven family proteins (TET) using alpha-ketoglutarate (AKG) as a cofactor. Here, we demonstrated that the circulatory AKG concentration was reduced in middle-aged mice (10-month-old) compared with young mice (2-month-old). Through AKG administration replenishing the AKG pool, aged mice were associated with the lower body weight gain and fat mass, and improved glucose tolerance after challenged with high-fat diet (HFD). These metabolic changes are accompanied by increased expression of brown adipose genes and proteins in inguinal adipose tissue. Cold-induced brown/beige adipogenesis was impeded in HFD mice, whereas AKG rescued the impairment of beige adipocyte functionality in middle-aged mice. Besides, AKG administration up-regulated Prdm16 expression, which was correlated with an increase of DNA demethylation in the Prdm16 promoter. In summary, AKG supplementation promotes beige adipogenesis and alleviates HFD-induced obesity in middle-aged mice, which is associated with enhanced DNA demethylation of the Prdm16 gene.
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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.