ArticleCell metabolism2010
Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis.
Article in Cell metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers.
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Who cites it
286 citing papers in PubMed, 506 citations in OpenAlex.
- SIRT6 Mediates Sterol-Dependent Feedback Regulation of Cholesterol Biosynthetic Genes in Hepatocytes.Biomolecules & therapeutics · 2026Article
- Hepatic SIRT6 Deficiency Accelerates Female-Specific Aging Through SULT1E1-Mediated Estrogen Depletion.International journal of molecular sciences · 2026Article
- Emerging roles of SIRT6 and its modulators in kidney diseases.Cell death discovery · 2026Review
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- The Sirtuin Network: Linking NADDiabetes/metabolism research and reviews · 2026Review
- Centenarian SIRT6 variants elevate SIRT6 protein and enhance cellular senescence resistance.Research square · 2026Article
- Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival.GeroScience · 2026Article
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- SOX4 induces cisplatin resistance in cervical cancer cells by inhibiting aerobic glycolysis.Cell death discovery · 2026Article
- Article
- Invited: Longitudinal Assessment of Diets with Varying Carbohydrate-to-Fat Ratios and Fiber Supplementation on Immunometabolic Markers, Liver Function, and Gut Microbiome.The Journal of nutrition · 2026Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- NADCommunications biology · 2025Article
- Bridging the gap in obesity research: A consensus statement from the European Society for Clinical Investigation.European journal of clinical investigation · 2025Review
- Review
- The SIRT6 Activator MDL-800 Inhibits PPARα and Fatty acid Oxidation-Related Gene Expression in Hepatocytes.Biomolecules & therapeutics · 2025Article
- Steatotic liver disease in metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor.Breast cancer research and treatment · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
226 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Under various conditions, mammals have the ability to maintain serum glucose concentration within a narrow range. SIRT1 plays an important role in regulating gluconeogenesis and fat metabolism; however, the underlying mechanisms remain elusive. Here, we show that SIRT1 forms a complex with FOXO3a and NRF1 on the SIRT6 promoter and positively regulates expression of SIRT6, which, in turn, negatively regulates glycolysis, triglyceride synthesis, and fat metabolism by deacetylating histone H3 lysine 9 in the promoter of many genes involved in these processes. Liver-specific deletion of SIRT6 in mice causes profound alterations in gene expression, leading to increased glycolysis, triglyceride synthesis, reduced beta oxidation, and fatty liver formation. Human fatty liver samples exhibited significantly lower levels of SIRT6 than did normal controls. Thus, SIRT6 plays a critical role in fat metabolism and may serve as a therapeutic target for treating fatty liver disease, the most common cause of liver dysfunction in humans.
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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.