S3QELs protect against diet-induced intestinal barrier dysfunction,Aging Cell

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S3QELs protect against diet-induced intestinal barrier dysfunction
Aging Cell ( IF 8.0 ) Pub Date : 2021-09-14 , DOI: 10.1111/acel.13476
Mark A Watson ₁ , Blaine Pattavina ₁ , Tyler A U Hilsabeck ₁ , Jose Lopez-Dominguez ₁ , Pankaj Kapahi ₁ , Martin D Brand ₁

Affiliation

The underlying causes of aging remain elusive, but may include decreased intestinal homeostasis followed by disruption of the intestinal barrier, which can be mimicked by nutrient-rich diets. S3QELs are small-molecule suppressors of site III_Qo electron leak; they suppress superoxide generation at complex III of the mitochondrial electron transport chain without inhibiting oxidative phosphorylation. Here we show that feeding different S3QELs to Drosophila on a high-nutrient diet protects against greater intestinal permeability, greater enterocyte apoptotic cell number, and shorter median lifespan. Hif-1α knockdown in enterocytes also protects, and blunts any further protection by S3QELs. Feeding S3QELs to mice on a high-fat diet also protects against the diet-induced increase in intestinal permeability. Our results demonstrate by inference of S3QEL use that superoxide produced by complex III in enterocytes contributes to diet-induced intestinal barrier disruption in both flies and mice.

中文翻译：

S3QEL 可预防饮食引起的肠道屏障功能障碍

衰老的根本原因仍然难以捉摸，但可能包括肠道稳态降低，随后肠道屏障被破坏，这可以通过营养丰富的饮食来模仿。S3QEL 是位点 III _Qo电子泄漏的小分子抑制剂；它们在不抑制氧化磷酸化的情况下抑制线粒体电子传递链复合物 III 处的超氧化物生成。在这里，我们展示了给果蝇喂食不同的 S3QEL高营养饮食可防止肠道通透性增加、肠细胞凋亡细胞数量增加和中位寿命缩短。肠细胞中的 Hif-1α 敲低也可以保护并削弱 S3QEL 的任何进一步保护。用高脂饮食给小鼠喂食 S3QELs 也可以防止饮食引起的肠道通透性增加。我们的结果通过推断 S3QEL 的使用表明，肠细胞中复合物 III 产生的超氧化物有助于饮食诱导的果蝇和小鼠肠道屏障破坏。

更新日期：2021-10-17

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