Study On The Preparation Of COSMG And Their Anti-obesity Effect And Mechanism

Obesity is a prevalent disease caused by excessive accumulation of fat in the body,which can lead to metabolic syndromes such as hypertension,coronary heart disease,type 2 diabetes,hyperlipidemia and nonalcoholic fatty liver,which seriously endangers human health.At present,the drugs related to weight loss and lipid-lowering basically have problems such as toxic side effects,ineffective efficacy,difficulty in development and reporting.Therefore,the research and development of a safe and effective weight loss product are of great significance to the cause of human health.Chitosan oligosaccharides(COS)is an oligomeric oligosaccharide with good biological activity,novel structure and few adverse reactions.Compared with chitosan,COS has higher water solubility and lower viscosity,which makes it easier to absorb passive objects and has higher bioavailability,making it a promising application in biomedicine and health foods.Our previous study found that COS has good weight loss activity.Therefore,this study first prepared chitosan oligosaccharides(COSM)with an average molecular weight of ≤3000 Da into granules(COSM granules,COSMG)and evaluated their quality.Then,the obese rat model induced by high-fat diet was used to evaluate the weight loss activity of COSMG,and its mechanism of action was discussed from the molecular biological level,which provided a scientific basis for the further development and utilization of COSMG.The optimal prescription: the binder is 5% PVP,the flavoring agent is 0.8% aspartame,the wetting agent is anhydrous ethanol,and COSMG is prepared by the wet method.According to COSM’s recommended daily dose of 3 g,taking 3 times a day,each package containing 1 g of COSM is packaged.The obese rat model induced by the high-fat diet was used to evaluate the weight loss activity of COSMG.The results are reflected in the following aspects:(1)COSMG can significantly inhibit the weight gain of rats,reduce the proliferation of adipose tissue and reduce the ratio of fat to the body,and show a better weight loss function without affecting appetite.(2)COSMG can significantly reduce serum TC,TG,and LDL-C levels,and increase HDL-C content,improving blood lipid levels in rats;(3)COSMG can significantly reduce the levels of AST and ALT in serum,reduce the liver weight of rats and reduce the content of TG,TC and FFA in liver,suggesting that COSMG can inhibit the lipid accumulation of liver tissue and have liver-protecting effect;(4)COSMG can increase the excretion of TC,TG and TBA in rat feces,suggesting that COSMG can help to improve the symptoms of obesity;(5)HE tissue sections show that COSMG has no toxic side effects on heart,liver,kidney and spleen.Through gene sequencing,it was found that there were 12970 common genes and 769 specific genes in the liver of the COSMG group and the Model group.Meanwhile,compared with the Model group,the number of genes up-regulated by the COSMG group was 55,and the number of down-regulated genes was 120.It is suggested that obese rats produce differential gene expression after COSMG administration;Gene Ontology analysis found that differential gene expression is mainly reflected in cellular protein binding and biomolecular component cell processes;KEGG pathway functional analysis of differential genes indicates that differential gene enrichment pathways are mainly involved in lipid metabolism,bile secretion and lipid synthesis.In order to elucidate the molecular mechanism of COSMG for preventing and improving obesity,this topic explored both liver endoplasmic reticulum stress and lipid metabolism.By using Real-time PCR and Western blotting,it was found that COSMG significantly down-regulated the expression of GRP78,XBP-1,ATF6,CHOP and SREBP2 gene in the liver of obese rats.At the same time,the expression levels of PPARα,LXRα,CYP7A1 gene were up-regulated.In summary,COSMG can effectively improve liver endoplasmic reticulum stress and regulate liver lipid metabolism,promote cholesterol conversion to bile acid,reduce lipid accumulation,thereby exerting its weight loss and lipid-lowering effects.