Research On Metabolism And Mechanism Of Bile Acid By Haw Pectin And Its Oligosaccharides In Mice

In this paper,we investigated the effects of haw pectin,haw pectin oligosaccharides and haw pectic pentasaccharides to investigate the regulation of cholesterol metabolism and bile acid synthesis,to determine the regulation of mechanism and its' control path,to provide the reliable theoretical basis for the application of haw pectin and oligosaccharides.In this study,four-weeks-old male mice are the experimental animals.High blood lipids and animal models were established by feeding high-cholesterol diet(HCD)and high-cholesterol diet added haw pectin oligosaccharides(HCD+HPPS).We analyzed the plasma of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)biochemical markers,the content of hepatic TG,TC,HDL-C,and the content of bile acid of liver,small intestine tissue,gallbladder,ileum and other tissues.On this basis,we investigated the levels of mRNA in the liver of Na+-dependent taurocholate transporter(Ntcp)and hepatocyte bile salt export pump(Bsep).We aslo investigated the mRNA levels in the ileum of ileum bile acid binding protein(Ibabp),small intestine apical sodium-dependent bile salt transporter(Asbt)and organic solute transporter(Ost?/?).From these,we analyzed Bile acid absorption and transport that related genes mRNA.At the same time we examined the mRNA levels that in the liver of liver X-receptor(Lxr?),farnesoid X-receptor(Fxr)and small heterodimer partner(Shp),and the mRNA levels of bile the small intestine Fxr and fibroblast growth factor(Fgf15).And then we analysised the regulation of levels of bile acid synthesis and regulation of that related gene mRNA.Finally,we investigated the various factors affecting the expression of CYP7A1,which is a key to enzyme of bile acid synthesis.Comparing with high fat control groups,pectin,pectin oligosaccharides,we found that pectin pentasaccharides could significantly decreased the level of cholesterol and triglyceride in serum and the effect of pectin pentasaccharide was the most significant.Pectin pentasaccharides significantly reduced arteriosclerosis index and free fatty acids,while the effects of pectin and pectin oligosaccharides reduction were not significant.The changes of high density lipoprotein cholesterol in each group were not significant.When compared with the high fat control,pectin pentasaccharides significantly increased the HDL-C / TC ratio.In the liver,pectin,pectin oligosaccharides and pectin pentasaccharides had reduced the role of total lipid,cholesterol and triglyceride levels.Pectin pentasaccharide was the most significant.The results of feces showed that pectin significantly increased the total fat,cholesterol and triglyceride content in feces comparing with the high fat group;Pectin pentasaccharides significantly increased the total fat content in the feces of mice;Pectin,pectin oligosaccharides and pectin pentasaccharides could increase the content of bile acids in feces,in which the effect of pectin oligosaccharides and pectin pentasaccharides were remarkable.Pectin pentasaccharides could significantly reduce bile acid levels of the liver and small intestine,improve bile acid levels of the gallbladder,and ultimately significantly reduce the level of the total bile acid pool.Comparing with HCD group,pectin pentasaccharides decreased the expression of Ntcp and Oatps in high fat mice,but it was not significant.Pectin pentasaccharides significantly increased the expression level of Bsep,decreased the expression levels of Ibabp and Ost?/? in high fat mice,and increased the expression of Asbt.Cyp7a1 was the starting enzyme for the conversion of cholesterol to bile acids and was also the rate-limiting enzyme.Hawthorn pectin pentasaccharides promoted the transcription of Cyp7a1 gene by promoting the expression of Lxr? and the transformation of cholesterol into bile acids.Hawthorn pectin pentasaccharides significantly reduced Fxr,Lhr and Shp levels,and increased the transcription level of Cyp7a1 gene by releasing the negative feedback control of Fxr/Shp molecular pathway.Comparing with the high fat group,pectin pentasaccharides significantly reduced Fxr,Fgf15 and Fgfr4 transcription levels,and relieved the negative feedback regulation of Fxr/Fgf15/Fgfr4 molecular pathway on Cyp7a1 and promoted cholesterol degradation.