Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria.
Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria.
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DOI：
10.1124/dmd.117.076612
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Shephard EA
中科院分区：
文献类型：
--
作者：
Scott F;Gonzalez Malagon SG;O'Brien BA;Fennema D;Veeravalli S;Coveney CR;Phillips IR;Shephard EA
我们以前已经确定了黄素含单加氧酶5（FMO 5）作为一种调节剂的代谢老化。本研究的目的是研究FMO 5在葡萄糖稳态中的作用，以及饮食和肠道植物群对FMO 5基因被破坏的小鼠（FMO 5 −/−小鼠）表型的影响。与野生型（WT）小鼠相比，Fmo 5 −/−小鼠对与年龄相关的葡萄糖稳态变化具有抵抗力，并保持了年轻动物特有的较高葡萄糖耐量和胰岛素敏感性。当喂食高脂肪饮食时，它们可以防止体重增加和胰岛素敏感性降低。Fmo 5-/-小鼠的表型与饮食和肠道微生物组无关，仅由宿主基因型决定。FMO 5 −/−小鼠具有与无菌小鼠相似的代谢特征，表明FMO 5在感知或响应肠道细菌方面发挥作用。在WT小鼠中，FMO 5存在于胃肠道的粘膜上皮中，在那里它响应于高脂肪饮食而被诱导。与WT小鼠相比，Fmo 5 −/−小鼠的结肠杯状细胞较少，并且它们在结肠激素抵抗素样分子β的产生方面存在差异。Fmo 5 −/−小鼠血浆中肿瘤坏死因子α浓度较低，附睾白色脂肪组织中补体成分3浓度较低，表明炎症程度改善。我们的研究结果暗示FMO 5作为体重和葡萄糖处置和胰岛素敏感性的调节剂，因此，确定FMO 5作为肥胖和胰岛素抵抗的潜在新的治疗靶点。
We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic aging. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5−/− mice). In comparison with wild-type (WT) counterparts, Fmo5−/− mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals. When fed a high-fat diet, they are protected against weight gain and reduction of insulin sensitivity. The phenotype of Fmo5−/− mice is independent of diet and the gut microbiome and is determined solely by the host genotype. Fmo5−/− mice have metabolic characteristics similar to those of germ-free mice, indicating that FMO5 plays a role in sensing or responding to gut bacteria. In WT mice, FMO5 is present in the mucosal epithelium of the gastrointestinal tract where it is induced in response to a high-fat diet. In comparison with WT mice, Fmo5−/− mice have fewer colonic goblet cells, and they differ in the production of the colonic hormone resistin-like molecule β. Fmo5−/− mice have lower concentrations of tumor necrosis factor α in plasma and of complement component 3 in epididymal white adipose tissue, indicative of improved inflammatory tone. Our results implicate FMO5 as a regulator of body weight and of glucose disposal and insulin sensitivity and, thus, identify FMO5 as a potential novel therapeutic target for obesity and insulin resistance.
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影响因子：
5.2
作者：
Kwon H;Pessin JE
通讯作者：
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深入了解erysipelotrichaceae在人类宿主中的作用。
影响因子：
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作者：
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通讯作者：
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DOI：
10.1111/j.1432-1033.1996.00683.x
发表时间：
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期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
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作者：
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作者：
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影响因子：
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作者：
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