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Updated: May 21, 2026
09:01
Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
Published on: March 10, 2015
Selenium-GPX4 axis orchestrates intestinal arachidonic acid metabolic reprogramming to mitigate inflammation
Chaohua Tang1, Huihui Tian1, Luxi Lin1
1State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Free Radical Biology & Medicine
|May 19, 2026
Summary
Dietary westernization worsens gut inflammation. Selenium supplementation, via glutathione peroxidase 4 (GPX4), mitigates inflammation by regulating arachidonic acid (AA) metabolism and oxylipin profiles, offering therapeutic strategies for inflammatory bowel diseases.
Area of Science:
- Gastroenterology and Immunology
- Metabolomics and Lipid Biology
Background:
- Dietary westernization and polyunsaturated fatty acids, like arachidonic acid (AA), are linked to intestinal inflammation.
- The precise mechanisms connecting AA-induced gut metabolic changes and GPX4-mediated inflammatory control need further investigation.
Purpose of the Study:
- To elucidate the mechanistic links between AA metabolism, gut dysregulation, and GPX4-driven inflammation.
- To evaluate the therapeutic potential of selenium (Se) supplementation in managing AA-induced intestinal inflammation.
Main Methods:
- Utilized lipopolysaccharide (LPS)-induced and chronic dietary AA-fed murine models.
- Employed genetic approaches (Gpx4+/-IEC, Gpx4+/-Mye) and single-cell RNA sequencing.
- Conducted ferrostatin-1 administration and intestinal epithelial cell-macrophage co-culture experiments.
Main Results:
- Selenium supplementation upregulated GPX4, alleviating AA-induced oxylipin alterations and inflammation.
- Intestinal epithelial cell GPX4 was identified as a key regulator of AA metabolic flux and inflammatory responses.
- GPX4 deficiency exacerbated AA-induced enterocyte loss, while ferrostatin-1 treatment ameliorated these effects.
- IEC-GPX4 corrected AA-induced oxylipin disturbances, suppressed inflammatory mediators, and prevented pro-inflammatory macrophage polarization.
Conclusions:
- The Se-GPX4-oxylipin axis is a critical regulatory circuit in intestinal inflammation.
- Targeting this axis offers promising, mechanistically grounded therapeutic strategies for inflammatory bowel diseases (IBD).
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