Zebrafish as an obesity model. Experimental setup (A). Comparison of the abdominal length and the abdominal fat between the normal group (NOR) and obesity group (OBS) stained with Nile red staining and observed under florescence microscope at day five of the experiment (B).

Screening of the D. kaki fruit extract for anti-insulin resistance activity in the zebrafish larvae. The treatment group with the D. kaki fruit extract significantly recovered, as shown by the PI size (A). Image of PI (pancreatic islet) staining by 40 µM 2-NBDG (B), normal (NOR), insulin induction (INS), and D. kaki (DK). #### p < 0.0001 compared to the control (NOR). ** p < 0.01 compared to insulin induction (INS). The statistical significance was determined using a one-way ANOVA with Dunnett’s post hoc test, expressed as means ± SEM (n = 20).

LC-ESI-MS/MS (A) and the expanded chromatogram created by plotting the total ion current in a series of product ions recorded as a function of the retention time of LC-ESI-MS/MS (B). LC+ESI-MS/MS (C) chromatograms of the D. kaki water extract and the expanded chromatogram created by plotting the total ion current in a series of product ions recorded as a function of the retention time of LC+ESI-MS/MS (D).

Mass spectrum of raffinose and gentiobiose from −ESI mode (A). Neokestose, melibiose, and sophorotriose from +ESI mode (B).

The crystallographic structure of PTP1B molecular docking related five oligosaccharides. Hydrogen bond of gentiobiose binding to the catalytic active sites of PTP1B Pro180, Cys215, and Ala217 residue of the catalytic WPD loop, catalytic domain, and catalytic loop, respectively (A). Melibiose showed ligand binding to Cys215 of the catalytic domain and Arg221 of the catalytic loop (B). Pro180 and Cys215 of the catalytic WPD loop and catalytic domain were bound to raffinose with hydrogen bonding (C). Neokestose and sophorotriose were not bound to any of the active residues (D).

Oligosaccharides from D. kaki significantly showed the recovery of β cells by decreasing the size of zebrafish PI (A). The images of 2-NBDG staining of PI (B), normal (NOR), insulin induction (INS), gentiobiose (GT), melibiose (MB), and raffinose (RF). #### p < 0.0001 compared to NOR. **** p < 0.0001, *** p < 0.001, ** p < 0.01 compared to INS. The statistical significance was determined using a one-way ANOVA with Dunnett’s post hoc test, expressed as means ± SEM (n = 20).

A total of 10 µg/mL of D. kaki (DK) and 1 µM of the oligosaccharides significantly decreased the abdominal size of and lipid accumulation in obese zebrafish by co-treatment (A). The images of 0.5 µg/mL Nile red staining of zebrafish body (B), normal (NOR), obesity induction (OBS), D. kaki (DK), gentiobiose (GT), melibiose (MB), and raffinose (RF). #### p < 0.0001 compared to NOR. **** p < 0.0001, *** p < 0.001, ** p < 0.01 compared to OBS. The statistical significance was determined using a one-way ANOVA with Dunnett’s post hoc test, expressed as means ± SEM (n = 20).

Gene expression on high-fat-diet-induced obesity in zebrafish larvae. The results of RT-qPCR evaluation on inflammatory-related genes TNF-α, IL-6, and IL-1β (A). The results of RT-qPCR evaluation on the lipogenesis-related genes SREBF1 and FASN (B). The results of RT-qPCR evaluation on lipid-lowering-related genes CPT1A (C). Normal (NOR), obesity induction (OBS), D. kaki (DK), gentiobiose (GT), melibiose (MB), and raffinose (RF). ### p < 0.001, ## p < 0.01 compared to NOR. *** p < 0.001, ** p < 0.01, * p < 0.05 compared to OBS. The statistical significance was determined using a one-way ANOVA with Dunnett’s post hoc test, expressed as means ± SEM (n = 20).