ArticleJCI insight2016
Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 5 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 5 syntheses or guidelines pooled it, 196 citations in OpenAlex.
- DNA methylation and type 2 diabetes: a systematic review.Clinical epigenetics · 2024Pooled it
- Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.American journal of human genetics · 2023Pooled it
- Research progress on the mechanism by which skin macrophage dysfunction mediates chronic inflammatory injury in diabetic skin.Frontiers in endocrinology · 2022Pooled it
- Immune responses to azacytidine in animal models of inflammatory disorders: a systematic review.Journal of translational medicine · 2021Pooled it
- Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review.Lipids in health and disease · 2019Pooled it
- DNMT1 facilitates the progression of metabolic dysfunction-associated steatotic liver disease by impeding transcription mediated by HNF4α and PPARα.Clinical and molecular hepatology · 2026Article
- Review
- The impact of inflammation, neuromodulation, and gut microbiota on developing cardiac fibrosis and hypertension.Cardiovascular research · 2026Review
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Article
- IL-Mediated Macrophage Polarization Axis: From Inflammatory Positive Feedback Loop to Precision Biomarkers and Therapeutic Targets for Allergic Rhinitis-A Narrative Review.Journal of asthma and allergy · 2026Review
- Macrophage Immunometabolism in Epicardial Adipose Tissue and Obesity-Related Atrial Fibrillation.Journal of inflammation research · 2026Review
- Revolutionizing Diabetic Foot Ulcer Management: Exploring the Therapeutic Potential of Natural Products.Current pharmaceutical design · 2026Review
- Bioinformatics analysis identifies key secretory protein-encoding differentially expressed genes in adipose tissue of metabolic syndrome.Adipocyte · 2025Article
- Nutri-epigenetics of mitochondrial function and energy homeostasis in obesity.Genes & nutrition · 2025Review
- Epigenetic programming of estrogen receptor in adipocytes by high-fat diet regulates obesity-induced inflammation.JCI insight · 2025Article
- Prominent fibroblast growth factor 21 with less abundant tumor-associated macrophages in hepatic mass of the conditional mgmt-deleted mice using LysM-Cre system.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence.Current issues in molecular biology · 2025Review
- Epigenetic regulation of nuclear receptors: Implications for endocrine-related diseases and therapeutic strategies.Genes & diseases · 2025Review
- Epigenetics and diabetic wound healing: Wilms tumor 1-associated protein as a therapeutic target.World journal of diabetes · 2025Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity is associated with increased classically activated M1 adipose tissue macrophages (ATMs) and decreased alternatively activated M2 ATMs, both of which contribute to obesity-induced inflammation and insulin resistance. However, the underlying mechanism remains unclear. We find that inhibiting DNA methylation pharmacologically using 5-aza-2'-deoxycytidine or genetically by DNA methyltransferase 1 (DNMT1) deletion promotes alternative activation and suppresses inflammation in macrophages. Consistently, mice with myeloid DNMT1 deficiency exhibit enhanced macrophage alternative activation, suppressed macrophage inflammation, and are protected from obesity-induced inflammation and insulin resistance. The promoter and 5'-untranslated region of peroxisome proliferator-activated receptor γ1 (PPARγ1) are enriched with CpGs and are epigenetically regulated. The saturated fatty acids stearate and palmitate and the inflammatory cytokine TNF-α significantly increase, whereas the TH2 cytokine IL-4 significantly decreases PPARγ1 promoter DNA methylation. Accordingly, inhibiting PPARγ1 promoter DNA methylation pharmacologically using 5-aza-2'-deoxycytidine or genetically by DNMT1 deletion promotes macrophage alternative activation. Our data therefore establish DNA hypermethylation at the PPARγ1 promoter induced by obesity-related factors as a critical determinant of ATM proinflammatory activation and inflammation, which contributes to insulin resistance in obesity.
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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.