| Obesity is a disease that manifests itself as metabolic disorder.It manifests as significant weight gain,excessive accumulation of body fat,increased blood lipids and abnormal body fat distribution.Increasing lipid synthesis and decreasing lipid breakdown can lead to obesity.Altering the composition and diversity of gut microbes can affect lipid metabolism and,in turn,obesity.SCFAs,metabolites of gut microbes,can also affect lipid metabolism,affecting obesity.Zfp217 which is a zinc finger protein with 8 C2H2 structures has been reported to be associated with the regulation of adipogenesis and differentiation.We have found that Zfp217+/-mice were able to resist obesity induced by high-fat diets.There are many studies have shown that genes interact with gut microbiota.It is unclear whether there are differences in intestinal composition between Zfp217+/-mice fed with high-fat diets and Zfp217+/+mice fed with high-fat diets,and whether Zfp217+/-mice improve lipid metabolism through by changing the composition of gut microbiota.We made 16S rRNA sequencing of Zfp217+/-mice and Zfp217+/+mice fed with high-fat diets.Then we measured the indicators related to fat metabolism,levels of inflammatory index and SCFAs.Finally,we analyzed the mechanism of gut microbiota resistance to obesity in Zfp217+/-mice.Our findings are as follows:1.The results of 16S rRNA sequencing showed significant differences in theβdiversity of gut microbiota between Zfp217+/-mice and Zfp217+/+mice（P<0.05）.Compared with Zfp217+/+mice,the relative abundance of Bacteroidetes in Zfp217+/-mice was significantly increased（P<0.05）,and F/B was significantly reduced（P<0.05）.LEf Se showed that AF12,Paraprevotella were significantly enriched in Zfp217+/-mice’s feces,and Roseburia,Dehalobacterium were significantly enriched in the Zfp217+/+mice’s feces（P<0.05）.The above results show that under the high-fat diet feeding,Zfp217 deletion changed the intestinal composition of mice.2.Our results showed that the total SCFAs level of intestinal contents in Zfp217+/-mice was significantly lower than that in the Zfp217+/+mice.（P<0.01）.The level of serum LDL-C in Zfp217+/-mice was significantly lower than that in the Zfp217+/+mice（P<0.05）.But the level of serum TNF-αin Zfp217+/-mice was significantly higher than that in the Zfp217+/+mice（P<0.05）.The relative m RNA level of IL-6 in Zfp217+/-mice,s duodenum was significantly higher than that in the Zfp217+/+mice（P<0.05）.The relative m RNA level of IL-17 and TNF-αin Zfp217+/-mice,s duodenum was significantly higher than that in the Zfp217+/+mice（P<0.05）.The relative m RNA level of IL-1β,IL-6,IL-2b,TNF-αin Zfp217+/-mice,s cecum were significantly lower than those in the Zfp217+/+mice（P<0.05）.The above results show that under high-fat diet feeding,Zfp217 deletion regulates the metabolic activity of intestinal microorganisms,significantly reduces the production of SCFAs and improves the inflammatory state of the intestine.3.The relative m RNA levels of ZO-2 in intestinal tissue in Zfp217+/-mice,s duodenum and colon were significantly higher than those in the control group（P<0.05）.The relative m RNA level of ZO-1 in Zfp217+/-mice,s cecum was significantly higher than that in Zfp217+/+mice（P<0.05）.In colon,the relative m RNA level of E-cadherin in Zfp217+/-mice was significantly higher than that in Zfp217+/+mice（P<0.01）.The above results show that Zfp217 is missing under high-fat diet feeding,which significantly improves intestinal barrier function.4.We did a Spearman correlation analysis and found that AF12 was negatively correlated with serum TNF-α,gut relative m RNA level of TNF-α,PPARγthat promotes the expression of fat differentiation and Adiponectin that promotes the expression of the lipid synthesis（P<0.05）.Roseburia was positively correlated with blood TG、T-CHO、TNF-α、gut TNF-α、PPARγthat promotes the expression of fat differentiation and AP2 that promotes the expression of the lipid synthesis（P<0.05）.In summary,under high-fat diets feeding,whole-body Zfp217-knockout significantly promoted the enrichment of AF12,Paraprevotella and other bacteria and inhibited the enrichment of Roseburia and other bacteria.It changed the composition of the gut microbiome,improved the function of the intestinal barrier and fights obesity. |
