Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-Ay mice

Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-Ay mice
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高脂肪饮食喂养的 KK-Ay 小鼠粪便中促炎挥发性代谢物水平升高

DOI:
10.1038/s41598-020-62541-7
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发表时间:
2020
期刊:
影响因子:
4.6
通讯作者:
Miyoshi Noriyuki
Miyoshi Noriyuki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Uchikawa Misaki;Kato Mai;Nagata Akika;Sanada Shunsuke;Yoshikawa Yuto;Tsunematsu Yuta;Sato Michio;Suzuki Takuji;Hashidume Tsutomu;Watanabe Kenji;Yoshikawa Yuko;Miyoshi Noriyuki

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当微生物组成恶化时,它会引发与几种生活方式相关的疾病(包括肥胖症和糖尿病)相关的低水平慢性炎症。粪便挥发性有机化合物(VOCs)已被发现在胃肠道疾病以及肠道感染不同。在这项研究中,为了评估生活方式相关疾病的发病机制与肠道中的VOC之间的潜在联系,从肥胖/糖尿病KK-Aymice(KK)或对照组的粪便中检测VOC。(C57 BL/6 J小鼠; BL)正常或高脂肪饮食采用顶空进样-GC-EI-MS研究了NFD或HFD。根据小鼠谱系(KK对BL)和饮食类型(NFD对HFD),粪便VOC谱的曲线清楚地将实验组分开。16 s rRNA序列分析表明,挥发性有机物的PCA分布与微区系组成基本一致。我们发现,一些挥发性代谢产物包括正烷烃醛(壬醛和辛醛),丙酮和苯酚在HFD和/或KK组显着增加。此外,这些挥发性代谢物在RAW 264鼠巨噬细胞系中诱导促炎活性,表明这些生物活性代谢物可能引发低水平慢性炎症。这些结果表明,在HFD喂养和/或糖尿病模型小鼠中检测到的促炎性VOC可能是糖尿病的新的非侵入性诊断生物标志物。
When the microfloral composition deteriorates, it triggers low-level chronic inflammation associated with several lifestyle-related diseases including obesity and diabetic mellitus. Fecal volatile organic compounds (VOCs) have been found to differ in gastrointestinal diseases as well as intestinal infection. In this study, to evaluate a potential association between the pathogenesis of lifestyle-related diseases and VOCs in the intestinal tract, fecal VOCs from obese/diabetic KK-Aymice (KK) or controls (C57BL/6J mice; BL) fed a normal or high fat diet (NFD or HFD) were investigated using headspace sampler-GC-EI-MS. Principal component analysis (PCA) of fecal VOC profiles clearly separated the experimental groups depending on the mouse lineage (KK vs BL) and the diet type (NFD vs HFD). 16 s rRNA sequencing revealed that the PCA distribution of VOCs was in parallel with the microfloral composition. We identified that some volatile metabolites includingn-alkanals (nonanal and octanal), acetone and phenol were significantly increased in the HFD and/or KK groups. Additionally, these volatile metabolites induced proinflammatory activity in the RAW264 murine macrophage cell line indicating these bioactive metabolites might trigger low-level chronic inflammation. These results suggest that proinflammatory VOCs detected in HFD-fed and/or diabetic model mice might be novel noninvasive diagnosis biomarkers for diabetes.
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