ArticleMolecular metabolism2025
Microglial ER stress response via IRE1α regulates diet-induced metabolic imbalance and obesity in mice.
Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Obesity-associated unfolded protein response, oxidative stress, and NRF2 signaling.International journal of obesity (2005) · 2026Review
- Gut microbiota dysfunction mediates stress-exacerbated aortic dissection via the bacteroides vulgatus-outer membrane vesicles-stearic acid-JNK/MAPK axis.Journal of nanobiotechnology · 2026Article
- Article
- Liver injury severity determines skeletal deterioration: a shared pathophysiological axis between MASLD and osteoarthritis.GeroScience · 2025Article
- Endoplasmic reticulum stress and unfolded protein response in immune cell function.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
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Abstract
backgroundChronic high-fat diet (HFD) feeding triggers hypothalamic inflammation and systemic metabolic dysfunction associated with endoplasmic reticulum (ER) stress. Glial cells, specifically microglia and astrocytes, are central mediators of hypothalamic inflammation. However, the role of Inositol-Requiring Enzyme 1α (IRE1α), a primary ER stress sensor, in glial cells and its contributions to metabolic dysfunction remains elusive.
objectivesTo investigate the role of IRE1α in microglia in mediating HFD-induced metabolic dysfunction.
methodsUsing novel conditional knockout mouse models (CX3CR1
resultsDeleting IRE1α in microglia significantly reduced LPS-induced pro-inflammatory cytokine gene expression in vitro. IRE1α deletion in microglia protected male mice from HFD-induced obesity, glucose intolerance, and hypothalamic inflammation, with no metabolic benefits observed in female mice. RNA-sequencing revealed significant transcriptional reprogramming of the hypothalamus, including upregulation of genes related to mitochondrial fatty acid oxidation, metabolic adaptability, and anti-inflammatory responses.
conclusionsOur findings reveal that IRE1α-mediated ER stress response in microglia significantly contributes to hypothalamic inflammation and systemic metabolic dysfunction in response to HFD, particularly in males, demonstrating an important role of microglial ER stress response in diet-induced obesity and metabolic diseases.
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