Anti-Diabetic Effects of Allulose in Diet-Induced Obese Mice via Regulation of mRNA Expression and Alteration of the Microbiome Composition

Figures

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  Figure 1. Effects of D-allulose supplement for 16 weeks, on body and adipocyte weights and plasma lipid levels, in C57BL/6J mice fed a high-fat diet. (A) Body weight. (B) Adipocyte weights. (C) Plasma lipid levels. (D) Adipokine levels. Data are presented as the mean ± SE. Kruskal-Wallis test; * p < 0.05, ** p < 0.01, *** p < 0.001 versus control; ND, normal diet; HFD, high-fat diet (20% fat, 1% cholesterol); ERY (HFD + 5% Erythritol); ALL, (HFD + 5% D-allulose); FFA, free fatty acid; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol, ApoA1, apolipoprotein A1; ApoB, apolipoprotein B; non-HDL-C = (TC) – (HDL-C), L:A ratio, leptin: adiponectin ratio.

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  Figure 2. Effect of 16-week D-allulose supplementation on insulin resistance-related biomarkers in C57BL/6J mice fed a high-fat diet. (A) Changes in FBG levels. (B) Intraperitoneal glucose tolerance test and area under the curve (AUC). (C) Plasma insulin, glucagon, and homeostatic model assessment of insulin resistance (HOMA-IR). (D) Hepatic glucose metabolism-related enzyme activity. (E) Plasma gastric-inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) levels. (F) Hepatic glycogen. (G) Immunohistochemistry staining for insulin and glucagon in the pancreas (200× magnification); Data are presented as the mean ± SE. Kruskal-Wallis test; * p < 0.05, ** p < 0.01, *** p < 0.001 versus control; ND, normal diet; HFD, high-fat diet (20% fat, 1% cholesterol); ERY (HFD + 5% Erythritol); ALL, (HFD + 5% D-allulose); FFA, free fatty acid; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol, ApoA1, apolipoprotein A1; ApoB, apolipoprotein B; non-HDL-C = (TC) – (HDL-C).

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  Figure 3. Effects of 16-week D-allulose supplement on hepatic steatosis-related markers in C57BL/6J mice fed a high-fat diet. (A) Hepatic lipid contents. (B) Liver weights. (C) Hepatic lipid metabolism-related enzyme activities. (D) Masson’s trichrome staining; (E) Plasma GOT and GPT levels; Data are presented as the mean ± SE. Kruskal-Wallis test; * p < 0.05, ** p < 0.01, *** p < 0.001 versus control; ND, normal diet; HFD, high-fat diet (20% fat, 1% cholesterol); ERY (HFD + 5% Erythritol); ALL, (HFD + 5% D-allulose); HMG-CoA reductase, hydroxy-methyl-glutaryl-coenzyme A reductase; ACAT, Acyl-CoA: cholesterol acyltransferase; GOT, glutamic-oxaloacetic transaminase; GPT, glutamic-pyruvic transaminase. Arrow indicates fibrosis signs (blue).

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  Figure 4. Gene transcription patterns related to inflammation in hepatic tissue. (A) Significant KEGG pathways. (B) The heatmap shows genes associated with the Toll-like receptor, NF-kappaB, PI3K-AKT, cytokine, and chemokine pathways. (C) Plasma inflammatory cytokine levels. Symbols in red were upregulated, whereas those in green were downregulated. Significant differences among the experiment groups are indicated; * p < 0.05, ** p < 0.01, *** p < 0.001; ND, normal diet (AIN-76); HFD, high-fat diet (AIN-76, 20% fat, 1% cholesterol); ERY (HFD + 5% Erythritol); and ALL, (HFD + 5% D-allulose).

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  Figure 5. Effects of 16-week D-allulose supplement on microbiota modulation. Relative abundance of Turicibacter, Coprococcus, Clostridiaceae and erysipelotrichaceae; Kruskal-Wallis test; * p < 0.05, ** p < 0.01, *** p < 0.001 versus control; ND, normal diet; HFD, high-fat diet (20% fat, 1% cholesterol); ERY (HFD + 5% Erythritol); ALL, (HFD + 5% D-allulose).