ArticleNature immunology2021
Macrophage IRX3 promotes diet-induced obesity and metabolic inflammation.
Article in Nature immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Review
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- Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation.Nature communications · 2026Article
- Influence of RNA Modifications on Cancer Metabolism: Interplay with Hypoxia and Therapeutic Implications.Advances in experimental medicine and biology · 2026Review
- IRX3-CDK14 axis promotes glioblastoma progression by regulating LRP6-mediated canonical Wnt/β-catenin pathway.Cell death & disease · 2025Article
- An atlas of ferroptosis-induced secretomes.Cell death and differentiation · 2025Article
- Article
- IRX3 controls a SUMOylation-dependent differentiation switch in adipocyte precursor cells.Nature communications · 2025Article
- Baf60c in skeletal muscle regulates adipose tissue thermogenesis via Musclin-mediated endocrine signaling.Life metabolism · 2025Article
- Targeted Delivery of α-ketoglutarate to Macrophages in Bone: A Novel Therapeutic Strategy for Improving Fracture Healing in Type 2 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- YTHDC2 manipulates anti-tumoral macrophage polarization and predicts favorable outcomes in triple negative breast cancer.NPJ precision oncology · 2025Article
- Macrophage SUCLA2 coupled glutaminolysis manipulates obesity through AMPK.Nature communications · 2025Article
- Siglec-E augments adipose tissue inflammation by modulating TRAF3 signaling and monocytic myeloid-derived suppressor cells during obesity.Frontiers in immunology · 2025Article
- Epigenetic Mechanisms in Osteoporosis: Exploring the Power of mJournal of cellular and molecular medicine · 2025Review
- CD169International journal of molecular sciences · 2024Article
- METTL3 and METTL14-mediated NScientific reports · 2024Article
- Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.Molecular biomedicine · 2023Article
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10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic inflammation is closely linked to obesity, and is implicated in the pathogenesis of metabolic diseases. FTO harbors the strongest genetic association with polygenic obesity, and IRX3 mediates the effects of FTO on body weight. However, in what cells and how IRX3 carries out this control are poorly understood. Here we report that macrophage IRX3 promotes metabolic inflammation to accelerate the development of obesity and type 2 diabetes. Mice with myeloid-specific deletion of Irx3 were protected against diet-induced obesity and metabolic diseases via increasing adaptive thermogenesis. Mechanistically, macrophage IRX3 promoted proinflammatory cytokine transcription and thus repressed adipocyte adrenergic signaling, thereby inhibiting lipolysis and thermogenesis. JNK1/2 phosphorylated IRX3, leading to its dimerization and nuclear translocation for transcription. Further, lipopolysaccharide stimulation stabilized IRX3 by inhibiting its ubiquitination, which amplified the transcriptional capacity of IRX3. Together, our findings identify a new player, macrophage IRX3, in the control of body weight and metabolic inflammation, implicating IRX3 as a therapeutic target.
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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.