AIMS Lipopolysaccharide (LPS)-induced intestinal injury is a common clinical feature of sepsis. Aggravated inflammation and higher sensitivity to infection are associated with high-fat diet (HFD) in patients with type 2 diabetes and/or obesity. However, the mechanism by which HFD exacerbates LPS-induced intestinal injury has not been elucidated. This study aims to examine the effects of HFD on intestinal injury induced by LPS and the underlying mechanism. MAIN METHODS Mice were fed with HFD or regular chow for 12weeks and were then challenged with LPS. Vas2870 was administered to mice that received HFD before the initiation of the diet. The levels of tight junction protein expression, oxidative stress, organ injury, and nicotinamide adenine dinucleotide phosphate (NADPH)-associated proteins were assessed periodically. KEY FINDINGS LPS treatment resulted in severe intestinal pathological injury and increased oxidative stress, evidenced by significantly increased serum diamine oxidase, reactive oxygen species, malondialdehyde, and intestinal fatty acid binding protein contents. Additionally, a decrease in tight junction protein expression was observed, indicating a loss of tight junction integrity. LPS treatment induced the expression of Nox2 and Nox4. All the effects were more severe in HFD mice. Treatment with vas2870 conferred protection against LPS-induced intestinal injury in HFD-fed mice, partially reduced oxidative stress, and rescued the expression of tight junction proteins. CONCLUSION HFD aggravated LPS-induced intestine injury through exacerbating intestinal Nox-related oxidative stress, which led to a loss of the integrity of tight junctions and consequently increased intestinal permeability.

中文翻译：

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高脂饮食会增加NADPH-氧化酶相关的氧化应激，并加重LPS诱导的肠损伤。

AIMS脂多糖（LPS）引起的肠损伤是败血症的常见临床特征。2型糖尿病和/或肥胖患者的高脂饮食（HFD）与炎症加剧和对感染的更高敏感性相关。但是，HFD加剧LPS引起的肠道损伤的机制尚未阐明。本研究旨在探讨HFD对LPS诱导的肠损伤的影响及其潜在机制。主要方法给小鼠喂HFD或常规食物12周，然后用LPS攻击。在开始饮食之前，将Vas2870给予接受HFD的小鼠。定期评估紧密连接蛋白的表达，氧化应激，器官损伤和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）相关蛋白的水平。主要发现LPS治疗导致严重的肠道病理损伤和氧化应激增加，血清二胺氧化酶，活性氧，丙二醛和肠道脂肪酸结合蛋白含量显着增加证明了这一点。另外，观察到紧密连接蛋白表达的降低，表明紧密连接完整性的损失。LPS处理诱导Nox2和Nox4的表达。所有的影响在HFD小鼠中更为严重。使用vas2870进行的处理可保护HFD喂养的小鼠免受LPS诱导的肠损伤，部分减轻氧化应激，并拯救紧密连接蛋白的表达。结论HFD通过加剧肠道Nox相关的氧化应激加剧LPS引起的肠道损伤，