Reactive oxygens species (ROS) are common byproducts of metabolic reactions and could be at the origin of many diseases of the elderly. Here we investigated the role of ROS in the renewal of the intestinal epithelium in mice lacking catalase (CAT) and/or nicotinamide nucleotide transhydrogenase (NNT) activities. mice have delayed intestinal epithelium renewal and were prone to develop necrotizing enterocolitis upon starvation. Interestingly, crypts lacking CAT showed fewer intestinal stem cells (ISC) and lower stem cell activity than wild-type. In contrast, crypts lacking NNT showed a similar number of ISCs as wild-type but increased stem cell activity, which was also impaired by the loss of CAT. No alteration in the number of Paneth cells (PCs) was observed in crypts of either or mice, but they showed an evident decline in the amount of lysozyme. deficiency caused fat accumulation in crypts, and a fall in the remarkable high amount of adipose triglyceride lipase (ATGL) in PCs. Notably, the low levels of ATGL in the intestine of Cat mice increased after a treatment with the antioxidant N-acetyl-L-cysteine. Supporting a role of ATGL in the regulation of ISC activity, its inhibition halt intestinal organoid development. These data suggest that the reduction in the renewal capacity of intestine originates from fatty acid metabolic alterations caused by peroxisomal ROS.

中文翻译：

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抗氧化活性的丧失通过改变脂质代谢来损害肠上皮稳态

活性氧（ROS）是代谢反应的常见副产物，可能是许多老年人疾病的根源。在这里，我们研究了活性氧在缺乏过氧化氢酶（CAT）和/或烟酰胺核苷酸转氢酶（NNT）活性的小鼠肠上皮更新中的作用。小鼠肠上皮更新延迟，并且在饥饿时容易发生坏死性小肠结肠炎。有趣的是，与野生型相比，缺乏 CAT 的隐窝显示出较少的肠干细胞 (ISC) 和较低的干细胞活性。相比之下，缺乏 NNT 的隐窝显示出与野生型相似数量的 ISC，但干细胞活性增加，但 CAT 的缺失也会损害干细胞活性。在小鼠隐窝中没有观察到潘氏细胞（PC）数量的变化，但溶菌酶的量明显下降。缺乏会导致隐窝中脂肪堆积，并且 PC 中脂肪甘油三酯脂肪酶 (ATGL) 的含量显着下降。值得注意的是，在用抗氧化剂 N-乙酰基-L-半胱氨酸治疗后，猫小鼠肠道中 ATGL 的低水平有所增加。 ATGL 在 ISC 活性调节中发挥作用，其抑制作用会阻止肠道类器官的发育。这些数据表明肠道更新能力的降低源于过氧化物酶体ROS引起的脂肪酸代谢改变。