Antidiabetic and Antiobesity effects of Chitooligosaccharide and Its Derivatives

Abstract

In this study, three derivatives of chitooligosaccharides (COS) which have already shown to have adipogenesis inhibitory effect where inhibition of adipogenesis and lipid accumulation is very important to prevent obesity and obesity-related diseases, especially diabetes which significantly increased all over the world recently, were synthesized through structural modification of ?OH and ?NH2 residues. Furthermore, antiobesity and antidiabetic effects of synthesized COS derivatives were compared with COS. COS remarkably decreased lipid accumulation, an indicator for adipogenesis, in 3T3-L1 adipocyte cells, where carboxylation and sulfation of COS increased adipogenesis inhibitory effect. Also mRNA expressions of adipogenic factors such as peroxisome proliferator-activated receptor (PPAR) gamma and sterol regulatory element-binding protein (SREBP) 1 were considerably decreased when compared between COS and its derivatives. Protein levels of PPAR-gamma and CCAAT/enhancer-binding protein (C/EBP) alpha, the key adipogenic factors, downregulated with COS derivative treatment, Moreover, only sulfation of COS moderately inhibited alpha-glucosidase and alpha-amylase activity which are important enzymes for controlling blood glucose in diabetic conditions, where COS and its carboxylation showed no effect. Besides, it has been seen that modified COSs have a little effect on inhibiting protein glycation where COS have no effect. As a result, structural modification of COS by carboxylation and sulfation increased its antiobesity effect. Additionally, sulfated COS showed antidiabetic activities unlike COS. These data indicate that COS derivatives have the potential to be used as additives in food industry or pharmaceuticals.