ArticleExperimental & molecular medicine2019
Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans.
Article in Experimental & molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- The persulfidome of alveolar epithelial cells reveals persulfidation of calprotectin as critical to preserve its antifungal activity.iScience · 2026Article
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- IMP2 enhances M2 macrophage polarization via LKB1-AMPK-mediated mitochondrial dynamics and fatty acid β-oxidation to ameliorate diabetic osteoporosis.Cellular and molecular life sciences : CMLS · 2026Article
- Sirt6 promotes tumor growth and suppresses immune surveillance.Cancer cell international · 2026Article
- Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling.Nature communications · 2026Article
- Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease.Renal failure · 2025Review
- PAK4 phosphorylates cyclin-dependent kinase 2 to promote the GExperimental & molecular medicine · 2025Article
- Long-Term In Vivo Administration of Panaxynol Alleviates Diabetes-Induced Vascular Calcification by Modulating Sirt6-Mediated sEH Function in Perivascular Adipose Tissue.Journal of agricultural and food chemistry · 2025Article
- Cytokine concentration in peripheral blood of patients with childhood obesity.Frontiers in immunology · 2025Article
- Impaired autophagy-mediated macrophage polarization contributes to age-related hyposalivation.Cell proliferation · 2024Article
- The multifaceted life of macrophages in white adipose tissue: Immune shift couples with metabolic switch.Immunological reviews · 2024Review
- Caffeic Acid Phenethyl Ester Suppresses Oxidative Stress and Regulates M1/M2 Microglia Polarization via Sirt6/Nrf2 Pathway to Mitigate Cognitive Impairment in Aged Mice following Anesthesia and Surgery.Antioxidants (Basel, Switzerland) · 2023Article
- Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation.Diabetes & metabolism journal · 2023Review
- Sirtuins in osteoarthritis: current understanding.Frontiers in immunology · 2023Review
- The many faces of SIRT6 in the retina and retinal pigment epithelium.Frontiers in cell and developmental biology · 2023Review
- Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective.Antioxidants (Basel, Switzerland) · 2022Review
- IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Sirtuins: Key players in obesity-associated adipose tissue remodeling.Frontiers in immunology · 2022Review
- NADTheranostics · 2022Article
- SIRT6 Widely Regulates Aging, Immunity, and Cancer.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Although sirtuin 6 (Sirt6) deficiency has previously been implicated in diet-induced obesity and systemic insulin resistance, the adipocyte-specific role of Sirt6 in the regulation of adipose tissue inflammation and systemic metabolic dysfunction in mice fed normal chow and in humans remains elusive. Here, using Adipoq-Cre-mediated adipocyte-specific Sirt6 knockout (aS6KO) mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild-type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in the adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of the canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue.
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