Abstract
Metabolic syndrome has become a global health care problem since it is rapidly increasing worldwide. The search for alternative natural supplements may have potential benefits for obesity and diabetes patients. Diospyros kaki fruit extract and its oligosaccharides, including gentiobiose, melibiose, and raffinose, were examined for their anti-insulin resistance and obesity-preventing effect in zebrafish larvae. The results show that D. kaki oligosaccharides improved insulin resistance and high-fat-diet-induced obesity in zebrafish larvae, evidenced by enhanced β-cell recovery, decreased abdominal size, and reduced the lipid accumulation. The mechanism of the oligosaccharides, molecular docking, and enzyme activities of PTP1B were investigated. Three of the oligosaccharides had a binding interaction with the catalytic active sites of PTP1B, but did not show inhibitory effects in an enzyme assay. The catalytic residues of PTP1B were typically conserved and the cellular penetration of the cell membrane was necessary for the inhibitors. The results of the mechanism of action study indicate that D. kaki fruit extract and its oligosaccharides affected gene expression changes in inflammation- (TNF-α, IL-6, and IL-1β), lipogenesis- (SREBF1 and FASN), and lipid-lowering (CPT1A)-related genes. Therefore, D. kaki fruit extract and its oligosaccharides may have a great potential for applications in metabolic syndrome drug development and dietary supplements.