Anti-Obesity Activity And Mechanism Of Chondroitin Sulfate In Sturgeon Skull

Chondroitin sulfate had many functional properties such as biocompatibility,anti-inflammatory,biodegradable,non-immunogenicity and non-toxicity.Chondroitin sulfate can be extracted from both terrestrial and marine organisms.Among them,marine organisms were widely used in the extraction of chondroitin sulfate with higher biosafety.Sturgeon cartilage,as a by-product of processing,had the characteristics of large quantity,low utilization rate,but rich in protein and chondroitin sulfate and other biological active substances.Chondroitin sulfate was extracted from sturgeon skull by dilute alkali-enzymatic hydrolysis method,and its anti-obesity activity was studied by animal model.Through the changes of intestinal flora and liver metabolic differences,the possible anti-obesity mechanism was explored.The main research contents are as follows:(1)The extraction rate of chondroitin sulfate from sturgeon skull by dilute alkali-enzymatic hydrolysis was 27.2%.Different concentrations of chondroitin sulfate extracted from hig h-fat diet animal models were found to significantly inhibit weight gain and improve impaired glucose and insulin tolerance in high-fat diet-induced mice without changing energy intake.The levels of liver triglyceride and total cholesterol were reduced and serum dyslipidemia was relieved.The results showed that chondroitin sulfate extracted from sturgeon skull had excellent anti-obesity activity.(2)The structural diversity of intestinal flora was increased by high dose(400 mg/kg body weight(BW)/day)of sturgeon chondroitin sulfate significantly in high-fat diet mice.It had significant effect on the species composition at phylum,family and genus level of intestinal microflora of mice.At phylum level,the abundance of Firmicutes was significantly increased.At the family level,the proportion of Enterobacteriaceae was reduced.In the genus,Escherichia-Shigella was significantly reduced.Functional prediction analysis showed that the differential genes mainly existed in metabolic pathways after chondroitin sulfate treatment in high-fat diet mice,and the proportion of carbohydrate metabolism was the largest,followed by cofactor,vitamin metabolism and amino acid metabolism.Lipid metabolism and energy metabolism data can be read up to 10~5.The results showed that the extract of chondroitin sulfate from sturgeon skull could significantly affect the intestinal flora of mice,and was closely related to obesity.(3)The UPLC-TOF(+/-)-MS/MS technique was used for untargeted metabonomics analysis of mouse liver.It was found that the liver metabolites of sturgeon chondroitin sulfate mice treated with high dose(400 mg/kg body weight(BW)/day)of high fat diet changed significantly.Data statistics showed that the distribution of samples within the group is concentrated,and the tendency of sample separation between different groups is obvious.Thirteen kinds of differential metabolites were found in negative ion mode,and three kinds of differential metabolites were found in positive ion mode(P<0.05,VIP>1).Including a variety of bile acids,arachidonic acid and unsaturated fatty acids and other compounds closely related to lipid metabolism.After chondroitin sulfate treatment,the biosynthesis pathway of unsaturated fatty acids,primary bile acid biosynthesis,taurine and hypotaurine metabolism in liver were significantly changed.These results suggested that extracts of chondroitin sulfate from sturgeon skull can improve liver metabolic disorder induced by high fat diet,providing a possible molecular mechanism for the anti-obesity effect of chondroitin sulfate.These results indicated that chondroitin sulfate from sturgeon skull had obvious anti-obesity activity in a dose-dependent manner.Further intestinal microbiota sequencing and metabonomics analysis showed that the anti-obesity effect of chondroitin sulfate was closely related to intestinal microbiota changes and metabolic regulation.This study provided a possible molecular mechanism for the effect of chondroitin sulfate on weight loss and lipid reduction,which increased the utilization value of sturgeon by-products and promoted the development of functional food related to fat reduction.