Institute of Interdisciplinary Integrative Medicine Research , Shanghai University of Traditional Chinese Medicine , Shanghai 201203 , China.
Department of Biochemistry and Molecular Biology , Bengbu Medical College , Anhui Province 233030 , China.
J Proteome Res. 2019 Apr 5;18(4):1703-1714. doi: 10.1021/acs.jproteome.8b00945. Epub 2019 Mar 11.
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.
肥胖症具有高度异质性，其病因包括遗传异常、能量失衡、肠道菌群失调或这三者的综合作用。肥胖易感（OP）和肥胖抵抗（OR）表型在啮齿动物中很常见，即使给予高脂肪饮食（HFD）也是如此。然而，其潜在机制在很大程度上尚不清楚。雄性 C57BL/6J 小鼠用标准饲料或 HFD 喂养 8 周。根据体重增加情况定义 OP 和 OR 小鼠，通过气相色谱-质谱代谢组学测序和盲肠内容物 16S rDNA 的焦磷酸测序对血清代谢物和肠道微生物进行综合分析。在 Con、OP 和 OR 组之间的比较中鉴定出 60 种差异代谢物，其中 27 种与 OP 相关。这些差异代谢物主要涉及糖酵解、脂质和氨基酸代谢以及 TCA 循环。同时，与 OR 或 Con 小鼠相比，OP 小鼠的肠道微生物群具有明显不同的特征，表现为厚壁菌门与拟杆菌门的比例降低，变形菌门增加。此外，OP 小鼠的肠道微生物改变与关键血清代谢物的变化相关。富含 Proteobacteria 门的 OP 富集 Parasutterella 与大多数代谢物相关，表明其在肥胖症中至关重要。OP 小鼠在代谢和肠道微生物群特征上存在明显差异，OP 相关代谢物和细菌对于理解肥胖症的发展具有重要意义。
