Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet
Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet
复制标题
高脂肪饮食下肥胖小鼠的代谢和肠道微生物特征
DOI：
10.1021/acs.jproteome.8b00945
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发表时间：
2019-04-01
影响因子：
4.4
通讯作者：
Li, Houkai
中科院分区：
文献类型：
--
作者：
Gu, Yu;Liu, Can;Li, Houkai
肥胖的特点是由于遗传异常、能量失衡、肠道生态失调或三者的结合而具有高度异质性。在啮齿类动物中经常观察到肥胖倾向（OP）和抗性（OR）表型，即使在那些给予高脂肪饮食（HFD）的啮齿类动物中也是如此。然而，潜在的机制在很大程度上是未知的。雄性C57BL/6J小鼠分别饲喂鼠粮和HFD 8周。根据体重增加来定义OP和OR小鼠，并通过基于气相色谱-质谱的代谢组学测序和盲肠内容物16S rDNA焦磷酸测序进行综合血清代谢和肠道微生物谱分析。在Con、OP和OR组的比较中，共鉴定出60种差异代谢物，其中27种与OP相关。这些差异代谢物主要参与糖酵解、脂质、氨基酸代谢和TCA循环。与此同时，OP小鼠的肠道菌群与OR或Con小鼠相比具有明显的差异，其中厚壁菌门与拟杆菌门的比例降低，变形菌门的比例增加。此外，OP小鼠肠道微生物的改变与关键血清代谢物的变化相关。来自变形菌门的富含op的副菌与大多数代谢物相关，表明它是肥胖所必需的。OP小鼠在代谢和肠道微生物谱上是不同的，OP相关的代谢物和细菌对理解肥胖的发展具有重要意义。
Obesity is characterized with high heterogeneity due to genetic abnormality, energy imbalance, gut dysbiosis, or a combination of all three. Obesity-prone (OP) and-resistant (OR) phenotypes are frequently observed in rodents, even in those given a high-fat diet (HFD). However, the underlying mechanisms are largely unknown. Male C57BL/6J mice were fed with chow or a HFD for 8 weeks. OP and OR mice were defined based on body weight gain, and integrated serum metabolic and gut microbial profiling was performed by the gas chromatography-mass spectroscopy-based metabolomic sequencing and pyrosequencing of 16S rDNA of cecum contents. A total of 60 differential metabolites were identified in comparisons among Con, OP, and OR groups, in which 27 were OP-related. These differential metabolites are mainly involved in glycolysis, lipids, and amino acids metabolism and the TCA cycle. Meanwhile, OP mice had a distinct profile in gut microbiota compared to those of OR or Con mice, which showed a reduced ratio of Firmicutes to Bacteroidetes and increased Proteobacteria. Moreover, the gut microbial alteration of OP mice was correlated with the changes of the key serum metabolites. OP-enriched Parasutterella from the Proteobacteria phylum correlated to most of metabolites, suggesting that it was essential in obesity. OP mice are distinct in metabolic and gut microbial profiles, and OP-related metabolites and bacteria are of significance for understanding obesity development.