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.