ArticleProceedings of the National Academy of Sciences of the United States of America2010
IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 247 citations in OpenAlex.
- Soluble interleukin-13rα1: a circulating regulator of glucose.American journal of physiology. Endocrinology and metabolism · 2017Trial
- Helminth infections and type 2 diabetes: a cluster-randomized placebo controlled SUGARSPIN trial in Nangapanda, Flores, Indonesia.BMC infectious diseases · 2015Trial
- Spatiotemporal atlas of pro-inflammatory NF-κB and anti-inflammatory STAT6 signaling using reporter mice during mRNA vaccination.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Role of Janus kinase-signal transducer and activator of transcription signaling pathway in hormonal cancer therapeutic resistance and lineage plasticity.Endocrinology · 2026Review
- Maternal undernutrition inhibits fetal rumen development: novel miRNA-736-mediated dual targeting of E2F2 and MYBL2 in sheep.Journal of animal science and biotechnology · 2026Article
- Obesity and type 2 diabetes as chronic inflammation: how does the cytokine evidence align?Frontiers in endocrinology · 2026Review
- How intense is high-intensity interval training? Biomarker responses and associations with training load and fitness.iScience · 2025Article
- The role of the IL-9‒NLRP3 axis in insulin resistance and adipose tissue inflammation during diet-induced obesity.Cellular & molecular immunology · 2025Article
- Role of the Th2-like Immune Response in Obesity: IL-4 as a Metabolic Regulator and IL-13 as an Effector of Muscle Energy Metabolism.Biomedicines · 2025Review
- Host environment shapes filarial parasite fitness and Wolbachia endosymbionts dynamics.PLoS pathogens · 2025Article
- Modulation of STAT6 signaling for hepatoprotection.Frontiers in pharmacology · 2025Review
- Dynamic Roles and Expanding Diversity of Adipose Tissue Macrophages in Obesity.Journal of obesity & metabolic syndrome · 2024Review
- Article
- Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure.Science advances · 2024Article
- Fasting and Glucose Metabolism Differentially Impact Peripheral Inflammation in Human Type 2 Diabetes.Nutrients · 2024Article
- Comprehensive Role of GDF15 in Inhibiting Adipogenesis and Hyperlipidemia, Enhancing Cardiovascular Health and Alleviating Inflammation in Metabolic Disorders.Current pharmaceutical design · 2024Review
- Immune system dysregulation in the pathogenesis of non-alcoholic steatohepatitis: unveiling the critical role of T and B lymphocytes.Frontiers in immunology · 2024Review
- STAT6 promoting oxalate crystal deposition-induced renal fibrosis by mediating macrophage-to-myofibroblast transition via inhibiting fatty acid oxidation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
85 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. Here, we demonstrate that the IL-4/STAT6 immune axis, a key pathway in helminth immunity and allergies, controls peripheral nutrient metabolism and insulin sensitivity. Disruption of signal transducer and activator of transcription 6 (STAT6) decreases insulin action and enhances a peroxisome proliferator-activated receptor α (PPARα) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPARα-regulated program of nutrient catabolism and attenuating adipose tissue inflammation. These findings have thus identified an unexpected molecular link between the immune system and macronutrient metabolism, suggesting perhaps the coevolution of these pathways occurred to ensure access to glucose during times of helminth infection.
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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.