Studies On The Mechanisms Underlying The Effects Of Alginate Oligosaccharides On The Disorders Of Glucose Lipid Metabolism And The Gut Microflora

Alginate oligosaccharides are marine oligosaccharides that are degraded from alginate by biological enzymes;it is β-D mannuronic acid(ManA)and its C-5 epimer A linear binary copolymer of α-L guluronic acid(GulA)connected by 1-4 glycosidic bonds.Alginate oligosaccharides has a low molecular weight and good water solubility.Existing studies have found that alginate oligosaccharides has the functions of enhancing immune function,reducing cholesterol,and anti-tumor.In addition,alginate oligosaccharides has a certain degree of sweetness like other oligosaccharides,and can replace edible sugars such as sucrose.It does not affect the original flavor of food and can effectively prevent obesity,hypertension,and diabetes.Therefore,alginate oligosaccharides has broad development prospects in the fields of drug research,functional food development,agriculture and other fields.However,the existing literature does not clarify the molecular mechanism of lipid-lowering and glucose-lowering.In this thesis,alginate oligosaccharides was used as the research object,and a mouse model of type 2 diabetes was established by high fat diet combined with a small dose of streptozotocin,and 250mg/kg/day,500mg/kg/day,1000mg/kg/day of alginate oligosaccharides were given to mice with type 2 diabetes.The results showed that alginate oligosaccharides can significantly reduce the total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)levels,atherosclerosis index(AI),and glucose levels,Aspartate aminotransferase(AST),alanine aminotransferase(ALT)in the serum of T2DM mice.At the same time,alginate oligosaccharides can reduce liver index.In addition,liver and kidney pathological results showed that alginate oligosaccharides can improve its lesions.Further,by examining the expression of glucose and lipid metabolism-related genes in the liver of each group of mice,it was found that alginate oligosaccharides can inhibit the phosphoenolpyruvate carboxyl group.Enzyme phosphoenolpyruvate carboxykinase(PEPCK)and glucose 6 phosphatase(G6Pase),3-hydroxy-3-methylacetyl-CoA reductase(HMGCE),SET and MYND domain-containing protein 3(SMYD3),sterol regulatory element binding protein-2(SREBP-2)up-regulates the expression of cholesterol 7-alpha hydroxylase(CYP7A1)and LDL-receptor(LDLR).The results of 16S rDNA sequencing of the intestinal contents of each group of mice showed that alginate oligosaccharides can affect the composition of the intestinal flora and the abundance of species distribution,and Alginate oligosaccharides can reduces the abundance of Firmicutes and Lachnospiraceae and Increase the abundance of Bacteroidetes,Bacteroidales_S24-7_group,Rikenellaceae,Prevotellaceae,and Lactobacillales in the intestine of type 2 diabetic mice.By measuring the content of short-chain fatty acids in the colon contents of mice,the results showed that Alginate oligosaccharides can increase the content of short-chain fatty acids in the intestine of type 2 diabetic mice.Oleic acid-induced HepG2 hepatocytes were used to construct a model of hepatocyte steatosis.By examining the lipid metabolism activity and the expression of related genes in the cells,it was found that fucoidan can inhibit the expression of SREBP-2,SMYD3,and SREBP-2 genes.Alginate oligosaccharides have a lipid-lowering effect.In this paper,the intestinal system is simulated in vitro to study the effect of alginate oligosaccharides on the intestinal flora of patients with non-alcoholic fatty liver disease to determine its regulating effect.The results showed that the intestinal flora of patients with nonalcoholic fatty liver disease could degrade and utilize alginate oligosaccharides,the average degradation rate was 75.1%,and the degradation rate was up to 92.7%.Alginate oligosaccharides can regulate the intestinal flora metabolites of patients with non-alcoholic fatty liver disease,resulting in more short-chain fatty acids such as acetic acid and propionic acid.In addition,Alginate oligosaccharides can effectively promote the proliferation of bifidobacteria and lactic acid bacteria in the intestinal flora.These results indicate that Alginate oligosaccharides has a good regulatory effect on the intestinal flora of patients with nonalcoholic fatty liver disease.