The Serum Metabonomic And Composition Of Gut Microbiota Study On Obesity-prone And Obesity-resistant Mice

Objective:Obesity and obese-related diseases are serious threat to human health. The energy imbalance is the main cause of obesity development, that is excessive energy intake and/or reduced energy expenditure. The etiology of obesity is complicated. It is proposed that both the environmental and genetic factors coordinately contribute to the formation of obesity.Interestingly, there are also interindividual differences in body weight gain among popμlation. Some individuals are resistant to obesity even though they live in similar environment and diet. Accordingly, people who are apt to development of obesity are defined as obesity-prone(OP), whereas those that are resistant to obesity development are recognized as obesity-resistant(OR). In animals, OP and OR are usually observed within the same strain which are fed with identical diet. However,the mechanisms underlying the OP and OR phenotypes are largely unclear. In current study, we intended to identify the metabolic and gut microbiota differences by comparing the serum metabolic profiles and gut microbiota between OP and OR mice with metabonomics.Methods:In this study, we first developed OP and OR mice with high fat diet(HFD). Then,we analyzed the serum metabolic profiles with gas chromatography mass spectroscopy(GC/MS)-based metabonomic approach, and the composition of gut microbiota by pyrosequencing of 16 S rDNA of gut bacteria.Resμlts:(1) We successf μ lly replicated the OP and OR phenotypes in C57BL/6J mice which are represented with significant differences in body weight, volume of white adipose tissue and serum lipids.(2) We identified a group of differential metabolites in serum between Con and HFD mice. These differential metabolites are involved in various metabolic pathways such as amino acids 、 gluconeogenesis 、 glycolysis 、 and fatty acids metabolismpathways.(3) We observed distinct separation in metabolic profiles between OP and OR mice, and identified a series of differential metabolites between them. These metabolites are involved in carbohydrates, amino acids, and fatty acids metabolism.Moreover, several differential metabolites which are associated with gut microbiota metabolism are observed between OP and OR mice, suggesting the involvement of gut microbiota in body weight modμlation.(4) The sequencing of 16 S rDNA of gut bacteria indicated the differences in composition of gut microbiota. Further analysis on the correlation between gut bacteria and metabolites discovered some bacteria were positively correlated body weight such as Porphyromonadaceae, Coriobacteriaceae, Lachnospiraceae,Sutterellaceae, Clostridium_XlVb, and Lactobacilus, while some were negatively correlated with body weight such as Rikenellaceae, Ruminococcaceae and Erysipelotrichaceae.Conclusions:Our current study showed the differences in metabolism and structure of gut bacteria between OP and OR mice. The development of OP phenotype may be associated with the abnormal metabolism in carbohydrate, amino acids and fatty acids,as well as the alterations in some gut microbiota.