Ginseng Soluble Dietary Fiber Reverses Obesity via the PPAR/AMPK Signaling Pathway and Improves Intestinal Flora in Mice

Abstract

Background: Ginseng soluble dietary fiber (GSDF) has been shown to have good physicochemical properties; however, its in vivo benefits in obesity are yet to be fully elucidated.

Methods: To explore this, C57BL/6J obese mice were given metformin hydrochloride and different doses of GSDF for 60 days. The levels of blood lipids and inflammatory factors were detected by ELISA, and the pathological alterations were detected through the application of HE staining. The level of adipose tissue protein in epididymis was detected by Western blotting and through the effects of 16S rRNA sequencing on gut microbiota.

Results: The results showed that GSDF significantly improved basal physiological indices, lipid levels, and serum cytokine levels in the obese mice. GSDF increased the expression levels of PPAR-γ, AMPK, and P-AMPK proteins, and lowered the expression of IL-1β, TNF-α, and other proteins in the adipose tissues of the epididymis, in turn inhibiting adipogenesis and ameliorating lipid metabolism disorders. By lowering the Firmicutes/Bacteroidetes ratio in the gut and altering the abundance of thick-walled bacteria and mycobacterium, the abundance of species such as Lactobacillus, Alloprevotella, and Faecalibaculum was altered to improve cecum health.

Conclusions: These results suggest that GSDF may have a positive effect on growth, obesity, and cecal health in obese mice.

Keywords: PPAR/AMPK; ginseng soluble dietary fiber; gut microbiota; metabolism; obesity.

Figure 1

Effect of GSDF on basic indicators in HFD-induced obese mice. (a) Effects of GSDF on morphology in mice; (b) fasting blood glucose; (c) body weight and rate of body weight gain; (d) spleen index; (e) liver index; (f) kidney index; (g) BAT. Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 8, means ± SEM); ### p < 0.001 vs. control group, * p < 0.05 vs. HFD group, ** p < 0.01 vs. HFD group, *** p < 0.001 vs. HFD group.

Figure 2

Effect of GSDF on serum cytokine and lipid in HFD-induced obese mice. (a) TC, (b) TG, (c) LDL-C, (d) HDL-C, (e) IL-1β, (f) IL-10. Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 8, means ± SEM); ## p < 0.01 vs. control group, ### p < 0.001 vs. control group, * p < 0.05 vs. HFD group, ** p < 0.01 vs. HFD group, *** p < 0.001 vs. HFD group.

Figure 3

Effect of GSDF on the regulation of WAT and testicular histopathology in HFD-induced obese mice. (a) eWAT index, (b), mWAT index, (c) colon length, (d) histopathology of eWAT tissue (scale bar = 25 μm and objective: 400×), (e) mice colon histopathology (scale bar = 25 μm and objective: 400×). Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 8, means ± SEM); ### p < 0.001 vs. control group, * p < 0.05 vs. HFD group, ** p < 0.01 vs. HFD group, *** p < 0.001 vs. HFD group.

Figure 4

Effects of GSDF on AMPK pathway in mice. (a) Western blot images; (b) relative expression of TNF-α/β-actin; (c) relative expression of IL-1β/β-actin; (d) relative expression of AMPK/β-actin; (e) relative expression of PPAR-γ/β-actin; (f) relative expression of p-AMPK/β-actin. β-actin was used as the internal control. Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 8, mean ± SEM); ### p < 0.001 vs. control group, ** p < 0.01 vs. HFD group, *** p < 0.001 vs. HFD group.

Figure 5

Effects of GSDF on the composition and diversity of intestinal flora in mice. (a) Alpha diversity analysis of intestinal flora in mice, (b), principal coordinate analysis (PCoA) showing the distances between different samples (Bray–Curtis distance, (c) statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 6, mean ± SEM); # p < 0.05 vs. control group, ## p < 0.01 vs. control group, ** p < 0.01 vs. HFD group, *** p < 0.001 vs. HFD group, & p < 0.05 vs. GSDF-L group, § p < 0.05 vs. GSDF-H group.

Figure 6

Effect of GSDF on the composition of intestinal flora at the portal level in mice. (a) Taxonomic composition at the phylum levels, (b) abundance comparison of major species at the phylum levels. Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 6, mean ± SEM); ## p < 0.01 vs. control group, * p < 0.05 vs. HFD group, ** p < 0.01 vs. HFD group, *** p < 0.001 vs. HFD group, & p < 0.05 vs. GSDF-L group, && p < 0.01 vs. GSDF-L group, &&& p < 0.001 vs. GSDF-L group.

Figure 7

Effect of GSDF on the composition of intestinal flora at the genus level in mice. (a) Heat map of relative abundance at genus level. (b) Histogram of species abundance by group at the genus level. (c) Histogram of species abundance by sample at genus level. Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 6, mean ± SEM).

Figure 8

LEfSe analysis of GSDF on intestinal flora in mice. Statistical significance was determined by a one-way analysis of variance (ANOVA). HFD, high-fat-diet group; MH, metformin hydrochloride group; GSDF-L, ginseng soluble dietary fiber low-dose group; GSDF-M, ginseng soluble dietary fiber medium-dose group; GSDF-H, ginseng soluble dietary fiber high-dose group; (n = 6, mean ± SEM).