ArticleeLife2025
Targeting IRE1α improves insulin sensitivity and thermogenesis and suppresses metabolically active adipose tissue macrophages in male obese mice.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Targeting the IRE1α/XBP1 pathway in type 2 diabetes mellitus: from ER stress signaling to therapeutic opportunity.Molecular biology reports · 2026Review
- Pharmacological Inhibition of Pyruvate Dehydrogenase Kinase 4 Enhances Insulin Sensitivity in Mouse Models of Diabetes and Obesity.Journal of obesity & metabolic syndrome · 2026Article
- Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity.Biomolecules · 2026Review
- Siglec-E deletion alters AT macrophages phenotypes, induces an inflammatory response, and adipogenesis during diet-induced obesity.International immunopharmacology · 2026Article
- Identification and Sorting of Adipose Inflammatory and Metabolically Activated Macrophages in Diet-Induced Obesity.Bio-protocol · 2025Article
- Epigenetic suppression of creatine kinase B in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation.Molecular metabolism · 2025Article
- Do Lifestyle Interventions Mitigate the Oxidative Damage and Inflammation Induced by Obesity in the Testis?Antioxidants (Basel, Switzerland) · 2025Review
- Endoplasmic reticulum stress and unfolded protein response in immune cell function.Frontiers in immunology · 2025Review
- Emerging role of IRE1α in vascular diseases.Journal of cell communication and signaling · 2024Review
- Metabolic-Associated Fatty Liver Disease: The Influence of Oxidative Stress, Inflammation, Mitochondrial Dysfunctions, and the Role of Polyphenols.Pharmaceuticals (Basel, Switzerland) · 2024Review
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9 authors.
Funding
Abstract
Overnutrition engenders the expansion of adipose tissue and the accumulation of immune cells, in particular, macrophages, in the adipose tissue, leading to chronic low-grade inflammation and insulin resistance. In obesity, several proinflammatory subpopulations of adipose tissue macrophages (ATMs) identified hitherto include the conventional 'M1-like' CD11C-expressing ATM and the newly discovered metabolically activated CD9-expressing ATM; however, the relationship among ATM subpopulations is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) is activated in the adipocytes and immune cells under obesity. It is unknown whether targeting IRE1α is capable of reversing insulin resistance and obesity and modulating the metabolically activated ATMs. We report that pharmacological inhibition of IRE1α RNase significantly ameliorates insulin resistance and glucose intolerance in male mice with diet-induced obesity. IRE1α inhibition also increases thermogenesis and energy expenditure, and hence protects against high fat diet-induced obesity. Our study shows that the 'M1-like' CD11c
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