Metabolic and gut microbial characterization of obesity-prone mice under high-fat diet.

Obesity is characterized with high heterogeneity due to genetic abnormality, energy imbalance and/or gut dysbiosis. Obesity-prone (OP) and -resistant (OR) phenotypes are frequently observed in rodents even under high-fat diet (HFD). However, the underlying mechanisms are largely unknown. Male C57BL/6J mice were fed with chow or HFD for 8 weeks. OP and OR mice were defined based on body weight gain, and an integrated serum metabolic and gut microbial profiling was performed by gas chromatography-mass spectroscopy-based metabolomic and pyrosequencing of 16S rDNA of cecum contents. Sixty 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 TCA cycle. Meanwhile, OP mice had distinct profile in gut microbiota compared to OR or Con mice, which showed reduced ratio of Firmicutes to Bacteroidetes and increased Proteobacteria. Moreover, gut microbial alteration of OP mice was correlated with the changes of the key serum metabolites. OP-enriched Parasutterella from Proteobacteria phylum correlated to most of metabolites, suggesting 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.