ArticleNature communications2018
Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
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- Expression Analysis of Mitochondrial Energy Metabolism-Related Genes Identifies IRS2 as a Key Modulator in M2 Synovial Macrophages of Osteoarthritis.Biomedicines · 2026Article
- Tributyltin Alters Hepatic Immune Microenvironment to ProMote Liver Fibrosis Progression in Rats.Toxics · 2026Article
- Macrophage plasticity in thyroid eye disease: dual effects of inflammation and fibrosis.Frontiers in immunology · 2026Review
- Insomnia Improved by Intravenous Mesenchymal Stem Cell Transplant: A Case Report.Sleep science (Sao Paulo, Brazil) · 2025Article
- Obesity-associated macrophages dictate adipose stem cell ferroptosis and visceral fat dysfunction by propagating mitochondrial fragmentation.Nature communications · 2025Article
- Linear association of the dietary index for gut microbiota with insulin resistance and type 2 diabetes mellitus in U.S. adults: the mediating role of body mass index and inflammatory markers.Frontiers in nutrition · 2025Article
- Dynamic Roles and Expanding Diversity of Adipose Tissue Macrophages in Obesity.Journal of obesity & metabolic syndrome · 2024Review
- Investigating CR1 as an indicated Gene for mild cognitive impairment in type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2024Article
- Unraveling the complex roles of macrophages in obese adipose tissue: an overview.Frontiers of medicine · 2024Review
- Crosstalk between MIR-96 and IRS/PI3K/AKT/VEGF cascade in hRPE cells; A potential target for preventing diabetic retinopathy.PloS one · 2024Article
- Article
- Combined Ingestion of Tea Catechin and Citrus β-Cryptoxanthin Improves Liver Function via Adipokines in Chronic Obesity.Nutrients · 2023Article
- Apple-shaped obesity: A risky soil for cytokine-accelerated severity in COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A miRNA/CXCR4 signaling axis impairs monopoiesis and angiogenesis in diabetic critical limb ischemia.JCI insight · 2023Article
- Heterogeneity of adipose tissue-resident macrophages-beyond M1/M2 paradigm.Diabetology international · 2023Review
- Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4.Nucleic acids research · 2023Article
- Identification of serum metabolome signatures associated with retinal and renal complications of type 2 diabetes.Communications medicine · 2023Article
- Regulation of the immune system by the insulin receptor in health and disease.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
M2a-subtype macrophage activation is known to be impaired in obesity, although the underlying mechanisms remain poorly understood. Herein, we demonstrate that, the IL-4/Irs2/Akt pathway is selectively impaired, along with decreased macrophage Irs2 expression, although IL-4/STAT6 pathway is maintained. Indeed, myeloid cell-specific Irs2-deficient mice show impairment of IL-4-induced M2a-subtype macrophage activation, as a result of stabilization of the FoxO1/HDAC3/NCoR1 corepressor complex, resulting in insulin resistance under the HF diet condition. Moreover, the reduction of macrophage Irs2 expression is mediated by hyperinsulinemia via the insulin receptor (IR). In myeloid cell-specific IR-deficient mice, the IL-4/Irs2 pathway is preserved in the macrophages, which results in a reduced degree of insulin resistance, because of the lack of IR-mediated downregulation of Irs2. We conclude that downregulation of Irs2 in macrophages caused by hyperinsulinemia is responsible for systemic insulin resistance via impairment of M2a-subtype macrophage activation in obesity.
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