| Autor: |
Ai-Zhi Lin, Xian Fu, Qing Jiang, Xue Zhou, Sung Hee Hwang, Hou-Hua Yin, Kai-Di Ni, Qing-Jin Pan, Xin He, Ling-Tong Zhang, Yi-Wen Meng, Ya-Nan Liu, Hammock, Bruce D., Jun-Yan Liu |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 11/26/2024, Vol. 121 Issue 48, p1-8, 43p |
| Abstrakt: |
Highsucrose diet (HSD) was reported as a causative factor for multiorgan injuries. The underlying mechanisms and therapeutic strategies remain largely uncharted. In the present study, by using a metabolomics approach, we identified the soluble epoxide hydrolase (sEH) as a therapeutic target for HSD-mediated gut barrier dysfunction. Specifically, 16-week feeding on an HSD caused gut barrier dysfunction, such as colon inflammation and tight junction impairment in a murine model. A metabolomics analysis of mouse colon tissue showed a decrease in the 5(6)-epoxyeicosatrienoic acid [5(6)-EET] level and an increase in soluble epoxide hydrolase, which is related to HSD-mediated injuries to the gut barrier. The mice treated with a chemical inhibitor of sEH and the mice with genetic intervention by intestinal-specific knockout of the sEH gene significantly attenuated HSD-caused intestinal injuries by reducing HSD-mediated colon inflammation and improving the impaired tight junction caused by an HSD. Further, in vitro studies showed that treatment with 5(6)-EET, but not its hydrolytic product 5,6-dihydroxyeicosatrienoic acid (5,6-DiHET), significantly ablated high sucrose-caused intestinal epithelial inflammation and impaired tight junction. Additionally, 5(6)-EET is anti-inflammatory and improves gut epithelial tight junction while 5,6-DiHET cannot do so. This study presents an underlying mechanism of and a therapeutic strategy for the gut barrier dysfunction caused by an HSD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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