Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.
Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.
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抗氧化药物tempol促进肠道菌群中的功能代谢变化。
DOI：
10.1021/acs.jproteome.5b00957
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发表时间：
2016-02-05
影响因子：
4.4
通讯作者：
Patterson AD
中科院分区：
文献类型：
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作者：
Cai J;Zhang L;Jones RA;Correll JB;Hatzakis E;Smith PB;Gonzalez FJ;Patterson AD
最近的研究已经确定了肠道微生物群在肥胖和相关代谢紊乱的发病机制和进展中的重要作用。抗氧化剂tempol被证明可以预防或减少小鼠的体重增加并调节肠道微生物群;然而，tempol调节宿主和肠道微生物群体重增加/减轻的机制尚未明确。在这里，我们显示tempol（0、1、10和50 mg/kg p.o.持续5天）以剂量依赖性方式减少盲肠细菌发酵并增加粪便能量排泄。基于肝脏1H NMR的代谢组学确定了糖原和葡萄糖的剂量依赖性降低，生糖和生酮活性（酪氨酸和苯丙氨酸）增强，以及糖酵解途径的激活增加。基于血清1H NMR的代谢组学表明，tempol促进增强葡萄糖催化剂。肝脏基因表达显著改变，表现为Pepck和G6 pase增加，Hnf 4a、ChREBP、Fabp 1和Cd 36 mRNA减少。在无菌小鼠中未观察到肝脏和血清代谢组学谱的显著变化，从而确立了肠道微生物群在介导tempol的有益代谢作用中的重要作用。这些结果表明，tempol调节肠道微生物群落及其功能，导致宿主能量可用性降低和肝脏代谢向更分解代谢状态的显著转变。
Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver 1H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum 1H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles were observed in germ-free mice thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function resulting in reduced host energy availability and a significant shift in liver metabolism towards a more catabolic state.