Study On The Anti-obesity Effect And Lipid-lowering Activity Of Chitosan With Different Average Molecular Weight And Different Molecular Configuration(???)

Obesity is caused by an imbalance between caloric intake and expenditure.In recent decades,it has become a worldwide burden to public health.However,though there are already so many kind of anti-obesity drugs,most of them are characterized with side effects,non-significant effect and rebound.Therefore,the study and application of weight-losing products are full of twists,as well as challenges.Chitosan,as the second most abundant polysaccharide in nature,is confirmed with anti-obesity activity,which attracts much attention.Average molecular weight and molecular conformation are two important indexs for the evaluation of chitosan,which affect the physical properties,chemical properties and physiological activity of chitosan.However,now most studies about the anti-obesity activity of chitosan haven't specified the average molecular weight and molecular conformation of the chitosan uesd in the study,and haven't compared the anti-obesity activity and lipid-lowering activity of chitosan with different average molecular weight and molecular conformation.In this study,a series of ?-??-chitosan with different average molecular weight(Mw)were prepared.Its fat-binding capacity,cholesterol-binding capacity,inhibitory effects to pancreatic lipase activity,inhibitory effects on cell proliferation and adipogenesis in 3T3-L1 cells and anti-obesity effects in high-fat diet-induced obese rats were studied.Rresearch results are as follows:(1)A biopharmaceutical model of the digestive tract was used to determine the fatand cholesterol-binding capacity of ?-and ?-chitosan.?-and ?-chitosan with different Mw(~1?~3?~5?~7?~9 kDa)were prepared by oxidative degradation assisted with microwave irradiation.The results showed that all of the ?-and ?-chitosan samples exhibited fat-and cholesterol-binding capacities.Within the testing range,1 g of ?-WSC sample could absorb 2–8 g of peanut oil or 50–65 mg of cholesterol,which are both significantly higher than the ability of cellulose to do the same.Meanwhile,both Mw and molecular conformation affect the binding capacity of chitosan,as ?-chitosan of ~3 kDa shows the highest fat-and cholesterol-binding capacities(7.08 g.g-1 and 63.48 mg.g-1,respectively),and the binding ability of ?-chitosan declines as its Mw increases or decreases from 3000 Da.(2)The pancreatic lipase assays were based on p-nitrophenyl derivatives.All the samples(?-chitosan of ~1?~3?~5?~7?~9 kDa and ~1800?~1500?~1200?~900?~600?~300 kDa and ?-chitosan of ~1?~3?~5?~7?~9 kDa)were proven to be able to inhibit pancreatic lipase activity to some extent.The inhibition ratio of all the samples are smaller than orlistat.While orlistat is proved to have some side effects,chitosan,as marine-derived active compounds,has better application prospects.(3)The effects of ?-and ?-chitosan with different Mw on cell proliferation and adipogenesis in 3T3-L1 cells,intracellular lipid accumulation,and the expression of C/EBP? were studied.The results presented that on the cellular level,chitosan could significantly inhibite 3T3-L1 preadipocytes into adipogenic differentiation and lipid accumulation process,reduce the concentration of TAG in mature adipocyte;on the gene level,chitosan could inhibit the expression of C/EBP?.(4)The anti-obesity effect and lipid-lowering activity of ?-chitosan with different Mw were studied using high-fat diet-induced obese rats model.The result indicated that all three samples(?-chitisan,?-chitosan oligosaccharide and a composite product,HY-1)could reduce the weight of obese rats with obvious appetite suppressant,reduce CHO level in the serum and improve LDL-C level in the serum.In general,the anti-obesity effect of the composite product was the best which even better than orlistat.This study affirmed the anti-obesity activity and lipid-lowering activity of chitosan,researched the relationship between its anti-obesity effect and its Mw and its molecular conformation,and explored its mechanism of reducing weight from the level of cells and gene.This study is of great significance for the utilization and pharmacological investigation of chitosan's anti-obesity effect and lipid-lowering activity.