Effects Of Intermittent Fasting On Glucose And Lipid Metabolism As Well As Gut Microbiota In High-fat Diet-induced Obesity Mice

Objective The aim of this study was to evaluate effects of intermittent fasting on body weight,glucolipid metabolism and gut microbiota in high-fat diet induced obesity(DIO)mice,as well as identifying the specific bacterium involved in this process.Methods At first,the DIO mice model was established with C57BL/6J mice.Then mice fed a low-fat or high-fat diet were subjected to ad libitum feeding or intermittent fasting(15 cycles of alternate-day fasting).Body weight and energy intake of mice were recorded daily.At the end of the experiment,samples of feces,blood,fat and liver were collected for the further test.Results(1)Intermittent fasting reduced body weight in DIO mice,but did not change cumulative energy intake.(2)Intermittent fasting decreased the multipoint blood glucose value and the area under the curve of intraperitoneal glucose tolerance test in DIO mice.In addition,intermittent fasting reduced the concentration of glycosylated hemoglobin A1 c and homeostasis model index of insulin resistance.(3)Intermittent fasting decreased the concentration of plasma total cholesterol,triglyceride and low-density lipoprotein,and increased the concentration of high-density lipoprotein in DIO mice.Furthermore,intermittent fasting ameliorated the severity of liver steatosis,and down-regulated expression of genes involved in lipid synthesis,transport and lipolysis.(4)Intermittent fasting reduced accumulation of various parts of fat in DIO mice.H&E stained slides of inguinal white adipose tissue presented the multilocular structure,a typical characteristic of beige adipocytes,was increased in DIO mice subjected to intermittent fasting intervention.Meanwhile,real-time quantitative Polymerase Chain reaction showed that the relative expression of uncoupling protein 1(Ucp1)m RNA was up-regulated,and immunohistochemical staining of UCP1 indicated that the number of cells,that expressing UCP1 was increased.(5)Intermittent fasting reduced the level of plasma lipopolysaccharide.16 S r DNA gene amplicon sequencing suggested that intermittent fasting did not change ACE index(reflecting richness of gut microbiota),but had a tendency to increase Simpson index(reflecting diversity of gut microbiota).Non-Metric Multi-Dimensional Scaling plot suggested that the community structure of DIO mice subjected to intermittent fasting intervention was closer to that of lean mice fed low-fat diets.MRPP analysis showed that intermittent fasting significantly altered the composition of gut microbiota.Species analysis at the phylum level presented that intermittent fasting notably reduced the ratio of Firmicutes to Bacteroidetes in DIO mice.Species analysis at the family level showed intermittent fasting reduced the relative abundance of Enterobacteriaceae in DIO mice.LEf Se analysis suggested the relative abundance of Allobaculum,a beneficial bacterium that could produce short-chain fatty acids,was significantly increased in DIO mice subjected to intermittent fasting intervention.Conclusion(1)This study confirms the beneficial effects of intermittent fasting on diet-induced obesity and metabolic dysfunction,without any differences in energy intake.(2)This study find that intermittent fasting promotes beiging of white adipose tissue,reduces metabolic endotoxemia and reverses gut microbiota dysbiosis in DIO mice.(3)This study supports the important role of gut microbiota in mediating intermittent fasting to reduce obesity and improve metabolism,and suggests that Allobaculum may be a specific bacterium involved in this process,thereby providing a new target for intermittent fasting to treat obesity...