Preliminary Study On The Mechanism Of Phloridzin Resistance To High Fat-induced Obesitybased On Gut Microbiota Andbile Acids Metabolism

Obesity has become a serious social problem,and it’s urgent to prevent its occurrence and development.Some literatures reported that phlorizin can resistance to dyslipidemia and abnormal weight.Therefore,this study combined with gut microbiotaand bile acids metabolism to study whether phlorizin can effectively resist the devel-opment of high fat-induced obesity in mice,and preliminary explore its mechanism.The results of phlorizin to resist obesity and chronic inflammation in the high fat-induced mice had be investigated.The effect of phlorizin resist the on high fat diet induced obesity and chronic inflammation was investigated.The weight of mice in HFDgroup reached 34.02±0.44 g in the later stage of experiment,and the weight gain rate reached 45.61 % in the whole experiment.For the mice in PHZ group and NCD group that the body weight was only29.50±0.71 g and 28.16±0.39 g,respectively,and the weight gain rate was only 20.24 % and13.59%,respectively.The serum lipid in the HFDgroup was abnormal.The triglyceride(TG),the cholesterol(TC)and the low density lipoprotein(LDL)were significant increase and the high density lipoprotein(HDL)was significant decrease.In addition,the mice in HFD group also showed severe insulin resistance.The serum lipid levels and insulin resistance in the PHZ group had be wellcontrolled and showed the same trend as the NCD group.The chronic inflammatory manifestations were observed in HFD mice.The inflammatory factors such as monocytechemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)had reached 431.18±5.78 pg/ml,0.95±0.02ng/L,144.55±6.15 pg/ml,respectively.Both of these inflammatory factors were significantly higher than the NCD group.But the PHZ group was significantly lower than the HFD group and the same as the NCD group.Probably due to nuclear factor-κB(HF-κB)and endotoxin(LPS)led to chronic inflammation in the HFD group.The results of gut microbiota in the three groups had be investigated.The results of principal component analysis(PCA),cluster analysis and heatmap showed that the gut microbiota in the HFD group were significantly different from the NCD group.The gut Microbiota in the PHZ group had be regulated and the results of PHZ group were between theHFD group and the NCD group.Then eleven gut microbiota biomarkers had be screened by relative abundance,effect size and differences.Finally,it was concluded that five genus levels of microorganisms may be associated with phlorizin resistance to high fat-induced obesity.Among them,phloridzin can reduce the relative abundance of Allobaculum and the harmful bacteria Desulfovibrio which had increased cause by high-fat diet,and can increase the relative abundance of Bacteroides,Lactobacillus and Ruminococcacea-UCG-014 which had increased cause by high-fat diet.The results of feces bile salts in the three groups had be investigated.The results of partial least squares discriminant analysis(PLS-DA)indicated that 9 kinds of bile acids that may be associated with high fat diet induced obesity and the effects by phlorizin.The 9 bile acids are: lithocholic acid(LCA),chenodeoxycholic acid(CDCA),deoxycholic acid(DCA),taurodehydrocholic acid(TDHCA),w cholesteric acid(w MCA),a rat Cholic acid(a MCA),b rat Cholic acid(b MCA),acetylcholine(ACA)and bile acid(CA).The content of these 9 feces bile acids in the HFD group was significantly higher than the NCD group and the PHZ group.In the PHZ group,these bile acids had a sharp rise and then returned to the same level as the NCD group.The results of Biomarker between the gut microbiota and feces bile salts had be investigated.Combined with the pearson correlation coefficient and redundancy analysis(R DA)method,the correlation between the two had be described.It had be found that all primary bile acids in feces were not significantly correlated with the gut microbiota Biomarker,while secondary bile acids had be showed a significant correlation with some gut microbiota Biomarker.Results: Long-term high-fat diet can lead to severe obesity and chronic inflammation,the phlorizin can effectively resist obesity and chronic inflammation.it is preliminarily conclusioned that phlorizin may regulate some of the microbes which have be disturbed by the high-fat diet in the gut microbiota and stimulate the metabolism of some bile acids to exert their biological activity against obesity.The correlation results preliminarily proved that primary bile acid metabolism may be directly affected by phlorizin stimulation and less associated with gut microbiota,while phlorizin may directly or indirectly regulate gut microbiota and secondary bile acids and both effects exist simultaneously.