ArticleScientific reports2016
SIRT3 Deficiency Induces Endothelial Insulin Resistance and Blunts Endothelial-Dependent Vasorelaxation in Mice and Human with Obesity.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Review
- Diabetic retinopathy: shaped by the "hidden hand" of post-translational modifications.Molecular neurodegeneration · 2026Review
- Sirtuins at the Interface of Glucose Metabolism, Diabetes, and Heart Failure: Metabolic Sensing in Cardiometabolic Disease.International journal of molecular sciences · 2026Review
- Endothelial FUNDC1 regulates metabolic reprogramming and the obesity-diabetes transition through the SIRT3/GATA2/endothelin-1 axis.Nature communications · 2026Article
- Review
- SIRT3 regulates PDHA1 acetylation in HUVECs to modulate inflammation and pyroptosis under clinorotation.iScience · 2025Article
- Vascular Endothelial NAMPT-Mediated NADAging cell · 2025Article
- Early-life exercise extends healthspan but not lifespan in mice.Nature communications · 2025Article
- Comparative Effects of Tumor Necrosis Factor Alpha, Lipopolysaccharide, and Palmitate on Mitochondrial Dysfunction in Cultured 3T3-L1 Adipocytes.Cell biochemistry and biophysics · 2025Article
- Design, Synthesis, and Biological Evaluation of Novel Hydroxytyrosol Derivatives as Protectors for Vascular Endothelium Against Lipid Overload.Drug design, development and therapy · 2025Article
- Sirt3 improves monosodium urate crystal-induced inflammation by suppressing Acod1 expression.Arthritis research & therapy · 2023Article
- A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation.International journal of molecular sciences · 2023Review
- SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance.Antioxidants (Basel, Switzerland) · 2022Article
- Emerging Roles of SIRT3 in Cardiac Metabolism.Frontiers in cardiovascular medicine · 2022Review
- Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases.Biomedicines · 2021Review
- The association between left ventricular mass index and serum sirtuin 3 level in patients with hypertension.Cardiovascular endocrinology & metabolism · 2021Article
- Acute glucose influx-induced mitochondrial hyperpolarization inactivates myosin phosphatase as a novel mechanism of vascular smooth muscle contraction.Cell death & disease · 2021Article
- Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity.Pharmacology research & perspectives · 2020Article
- β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.American journal of physiology. Endocrinology and metabolism · 2020Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Recent evidence implicates the critical role of Sirtuin 3 (SIRT3) in the development of many metabolic diseases, but the contribution of SIRT3 to vascular homeostasis remains largely unknown. The aim of this study was to investigate the role of SIRT3 in endothelial insulin resistance and vascular dysfunction in obesity. We found an impaired insulin-induced mesenteric vasorelaxation and concomitant reduced vascular SIRT3 expression in morbid obese human subjects compared with the non-obese subjects. Downregulation of SIRT3 in cultured human endothelial cells increased mitochondrial reactive oxygen species (mtROS) and impaired insulin signaling as evidenced by decreased phosphorylation of Akt and endothelial nitric oxide synthase and subsequent reduced nitric oxide (NO) release. In addition, obese mice induced by 24-week high-fat diet (HFD) displayed an impaired endothelium-dependent vasorelaxation to both insulin and acetylcholine, which was further exacerbated by the gene deletion of Sirt3. Scavenging of mtROS not only restored insulin-stimulated NO production in SIRT3 knockdown cells, but also improved insulin-induced vasorelaxation in SIRT3 knockout mice fed with HFD. Taken together, our findings suggest that SIRT3 positively regulates endothelial insulin sensitivity and show that SIRT3 deficiency and resultant increased mtROS contribute to vascular dysfunction in obesity.
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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.