Acute low-dose endotoxin treatment results in improved whole-body glucose homeostasis in mice.
Acute low-dose endotoxin treatment results in improved whole-body glucose homeostasis in mice.
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DOI：
10.1016/j.metabol.2016.12.008
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Hulver MW
中科院分区：
文献类型：
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作者：
Stevens JR;McMillan RP;Resendes JT;Lloyd SK;Ali MM;Frisard MI;Hargett S;Keller SR;Hulver MW
与健康、正常体重的个体相比，肥胖个体呈现出增加的炎症性音调，这与胰岛素抵抗相关。假设导致肥胖和糖尿病状态下炎症增加的一个因素是血液内毒素水平升高，这种情况称为代谢性内毒素血症。在非肥胖和胰岛素敏感的个体中，循环内毒素浓度在一天中波动，餐后状态升高，吸收后状态恢复到基线水平。有证据表明，高脂肪喂养改变了这些波动，导致内毒素水平全天保持在高水平。内毒素水平改变对葡萄糖代谢的影响尚不清楚。本研究的目的是确定短期和长期内毒素（脂多糖，LPS）低幅度增加对人原代细胞系中葡萄糖耐量和胰岛素信号传导的影响，以及短期内毒素治疗对C57/B16小鼠模型中葡萄糖稳态的影响。首先，我们测试了短期低剂量内毒素治疗将增加胰岛素信号传导和糖原合成，而长期治疗将破坏细胞培养模型的假设。其次，我们检查了这些短期低剂量内毒素治疗是否有助于小鼠模型中全身葡萄糖稳态的类似改善。与我们最初的假设相反，短期内毒素处理对胰岛素信号传导或糖原合成没有影响，然而长期处理确实降低了糖原合成（P<0.05）。有趣的是，短期内毒素处理导致小鼠模型中葡萄糖稳态的显著改善（P<0.01）;这被认为至少部分归因于LPS对肝脏葡萄糖产生的抑制作用。这项研究表明，LPS的低幅度，短期变化可以对全身葡萄糖代谢产生显着影响，这可能是通过其对肝脏的直接作用而发生的。进一步的研究是必要的，以了解负责改变葡萄糖代谢的机制，以响应低幅度的变化，LPS水平。
Obese individuals present with an increased inflammatory tone as compared to healthy, normal-weight individuals, which is associated with insulin resistance. One factor hypothesized to contribute to increased inflammation in obese and diabetic states is elevated blood endotoxin levels, a condition known as metabolic endotoxemia. In non-obese and insulin sensitive individuals, circulating endotoxin concentrations fluctuate over the course of the day with elevations in the post-prandial state that return to baseline levels in the post-absorptive state. Evidence suggests that high-fat feeding alters these fluctuations causing endotoxin levels to remain high throughout the day. The effects of alterations in endotoxin levels on glucose metabolism are not clearly understood. The goal of this study was to determine the effects of both short-term and long-term increases in endotoxin (lipopolysaccharide, LPS) of a low magnitude on the glucose tolerance and insulin signaling in a human primary cell line as well as the effects of short-term endotoxin treatments on glucose homeostasis in a C57/Bl6 mouse model. First, we tested the hypothesis that short-term low-dose endotoxin treatments would augment insulin signaling and glycogen synthesis while long-term treatments would be disruptive in the cell culture model. Second, we examined if these short-term low dose treatments of endotoxin would contribute to similar improvements in whole-body glucose homeostasis in a mouse model. Contrary to our initial hypothesis, short-term endotoxin treatment had no effect on insulin signaling or glycogen synthesis, however long-term treatment indeed decreased glycogen synthesis (P<.05). Interestingly, short-term endotoxin treatment resulted in significant improvements in glucose homeostasis in the mouse model (P<.01); which is believed to be at least partly attributed to an inhibitory action of LPS on liver glucose production. This research shows that low-magnitude, short-term changes in LPS can have significant effects on whole body glucose metabolism and this likely occurs through its direct actions on the liver. Additional studies are necessary to understand the mechanisms responsible for altered glucose metabolism in response to low magnitude changes in LPS levels.