Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet

Silje Harvei, V. Skogen, Bjørg Egelandsdal, Signe Birkeland, Jan Erik Paulsen, Harald Carlsen
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Abstract

Lipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named “metabolic endotoxemia.” This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet.We supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks (n = 16–17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay.Our results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet.
长期口服 LPS 不会增加西式饮食小鼠的炎症反应或诱发代谢失调
据认为,食用高脂肪饮食后,肠道中的脂多糖(LPS)会进入血液,并通过一种名为 "代谢内毒素血症 "的过程引起全身炎症和代谢失调。本研究旨在确定小鼠口服 LPS 在饮食诱导的慢性低度炎症早期阶段的作用。我们给喂食高脂西式饮食(WSD)或标准饲料(SC)7 周的小鼠(n = 16-17)的饮用水中补充了大肠杆菌衍生的 LPS。每周记录体重。通过在不同时间点对 NF-κB 活性进行体内成像评估全身炎症状态,并在研究接近尾声时通过胰岛素敏感性测试和葡萄糖耐量测试评估葡萄糖失调。通过量化血浆中的 LPS 结合蛋白(LBP)和 LPS 抗体,以及直接使用 LPS 敏感细胞报告试验,间接估算了全身 LPS 暴露量。我们观察到,在两种饮食组中,肝脏区域的 NF-κB 活性都出现了短暂的 LPS 依赖性上调,这种反应在给予 LPS 后的第一周内消失,并在研究的其余时间内保持在较低水平。然而,在所有时间点,WSD喂养的小鼠的NF-κB活性都高于SC喂养的小鼠,与LPS给药无关。我们的研究结果表明,口服 LPS 对以西式高脂饮食喂养的小鼠的全身性炎症和代谢失调影响有限甚至没有影响,我们质疑肠道衍生的 LPS 是否有能力通过健康且未受损的肠道引发全身性炎症,即使暴露于高脂饮食中也是如此。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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