Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet

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.