| Obesity is a chronic nutritional disease caused by the energy metabolism out of balance, and it is harmful to public health. There are few anti-obesity drugs, and they have little efficacy and many side effects. It is difficult to develop and declare a new drug, so it is full of opportunities and challenges in market for drug research and development.Chitosan(CTS) is a kind of polysaccharide with high biological activity. Chitosan oligosaccharides(COS) is a king of oligosaccharide which have high biological activity, novel structure and less adverse reaction, and conformed to the characteristics of anti-obesity treatment which needs long-term medication. COS is promising in the field of weight lossing. We made COS(the number average molecular weight≤1000Da, COST) and CTS into capsules, then researched their preparation methods and quality standard. The nutritional animal model for obesity was established. These obese rats were administrated drugs by gavage for eight weeks, to evaluate the weight loss function of COSC and CTSC, compared the weight function ability of COSC to CTSC, explore their active effect of reducing weight.It indicated capsules were neat, stable when environment temperature was 20 to 25℃, humidity was 40% or less. The content uniformity, disintegration time and dissolution of COSC meet the requirements of Chinese Pharmacopeia. The content of COSC was 90.43%, meet the set requirement; moisture was 8.09%, meet health food requirement. The content uniformity, disintegration time and dissolution of CTSC meet the requirements of Chinese Pharmacopeia. The content of CTSC was 92.66%, meet the set requirement; moisture was 6.16%, meet health food requirement.COSC could reduce weight gain and the body fat very well in obese rats with no impact on appetite. It showed positive effect on weight control. COSC could significantly reduce the content of serum T-CHO, TG and LDL-C, increase HDL-C. It showed positive effect on lipid-lowing. Compared with Orlistat, there was no significantly difference on weight gain in COSC-H and COSC-M. Their effects on weight reducing were equal. COSC could improve fatty liver very well, suppress the expansion and proliferation of adipocytes in obese rats. COSC were safe to animals.CTSC could also significantly alleviate rats’ weight gain and body fat ratio without influence on appetite, showing positive of weight reducing. CTSC could decrease serum T-CHO, TG and LDL-C, increase serum HDL-C, in CTSC-H and CTSC-M groups. It indicated high dosage might improve blood lipid level. CTSC could restrain body weight gain and there was no significant difference between Orlistat. Their effects on reducing weight were equal. CTSC could alleviate fatty liver and inhibit the growth of adipocytes in obese rats. CTSC were safe to animals.The ability on weight control of COSC was better than CTSC. The effect on improving serum lipid of COSC was better than CTSC.There were 965 genes expressed differentially in COST group by gene sequencing of COST group, including eight significant enrichment pathways, such as metabolic pathway, steroid hormone biosynthesis pathway, bile secretion pathway, primary bile acid biosynthesis pathway, retinol metabolism pathway, unsaturated fatty acid biosynthesis pathway, PPAR signaling pathway, etc. The expressions of LXRα and PPARγ mRNA in epididymal adipose tissue of rats were detected by FQRT-PCR. The results showed that COST could inhibit the expression of LXRα, then down-regulated the expression of PPARγ to regulate lipid metabolism, storage and transportation. It could reduce lipid accumulation and differentiation in adipose tissue to exert its effect on reducing weight. |
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