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. 2022 Jul 1;14(13):2749.
doi: 10.3390/nu14132749.

GOS Ameliorates Nonalcoholic Fatty Liver Disease Induced by High Fat and High Sugar Diet through Lipid Metabolism and Intestinal Microbes

Shuting Qiu  1   2 , Jiajia Chen  1   2 , Yan Bai  3 , Jincan He  3 , Hua Cao  4 , Qishi Che  5 , Jiao Guo  2 , Zhengquan Su  1   2
Affiliations

GOS Ameliorates Nonalcoholic Fatty Liver Disease Induced by High Fat and High Sugar Diet through Lipid Metabolism and Intestinal Microbes

Shuting Qiu et al. Nutrients. .

Abstract

The treatment of nonalcoholic fatty liver disease (NAFLD) remains very challenging. This study investigated the therapeutic effect of galactose oligosaccharide (GOS), an important prebiotic, on NAFLD through in vivo and in vitro experiments and preliminarily explored the mechanism by which GOS improves liver lipid metabolism and inflammation through liver and intestinal microbiological analysis. The results of mouse liver lipidomics showed that GOS could promote body thermogenesis in mice with high-fat and high-sugar diet (HFHSD)-induced NAFLD, regulate lipolysis in liver fat cells, and accelerate glycine and cholesterol metabolism. GOS dose-dependently reduced the contents of total cholesterol (TC) and triglyceride (TG) in cells and reduced the accumulation of lipid droplets in cells. GOS also reduced the Firmicutes/Bacteroidetes ratio and altered the composition of the intestinal microbiota in mice fed a HFHSD. GOS can improve liver lipid metabolism and intestinal structure of NAFLD. These results provide a theoretical and experimental basis supporting the use of GOS as a health food with anti-NAFLD functions.

Keywords: galactose oligosaccharide; inflammation; intestinal microbes; lipid metabolism; nonalcoholic fatty liver disease; prebiotics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Experimental Design of NAFLD Mice.
Figure 2
Figure 2
Average food intake of mice in each group during 12 weeks of administration (a) and weekly food intake of mice during the administration period (b), weekly body weight of mice changed after administration (n = 10, mean ± SEM).
Figure 3
Figure 3
(A) Changes of TC (a), TG (b), HDL-C (c), LDL-C (d), and FFA (e) in serum of mice after administration (n = 10, mean ± SEM). (B) Changes in serum AST (a), ALT, (b) TNF-α (c), IL-6 (d), and IL-10 (e) of mice after administration (n = 10, mean ± SEM). (C) Changes of fasting blood glucose (a) and insulin in mice after administration (b) (n = 10, mean ± SEM). Changes in glucose tolerance of mice after administration (n = 6, mean ± SEM): (c) Blood glucose changes over time; (d) Area under GLU. Note: * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the model group.
Figure 4
Figure 4
(A) Changes in the levels of TC (a), TG (b), LDL-C (c), and HDL-C (d) in the liver of rats after administration. (B) Changes in the levels of MDA (a), SOD (b), GSH-Px (c), and CAT (d) in the liver of mice after administration. (C) Mice liver index after administration. (D,E) H&E staining and oil red O staining (200×, scale bar 50 μm) (n = 10, mean ± SEM). (F) Mice NAS scoring (n = 5). (G) The ratio of lipid accumulation area to total liver area in the liver (n = 5, mean ± SEM). Note: * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the model group.
Figure 5
Figure 5
(A) OPLS-DA score plot (a) and PCA plot (b) of liver tissue samples from the Control group and the Model group; (B) OPLS-DA score plot (a) and PCA plot (b) of liver tissue samples from the GOS group and the model group.
Figure 6
Figure 6
(A) Metabolite KEGG enrichment diagram of liver tissue samples in control and model. (B) Metabolite KEGG enrichment diagram of liver tissue samples in GOS and model. Venn diagram of metabolites in different groups where the Rich Factor was the ratio of the number of metabolites in the corresponding pathway to the total number of metabolites annotated by the detection of that pathway. The larger the value was, the greater the enrichment degree was. (C) Venn diagram of metabolites in different groups.
Figure 7
Figure 7
(A) Effects of GOS on the expression levels of FAS (a), SREBP-1C (b), ACC1 (c), PPARα (d), and SCD1 (e) genes in mice liver (n = 6, mean ± SEM). (B) Effects of GOS on the expression of PPARγ1 (a), PPARγ2 (b), IL-1β (c), TNF-α (d), and IL-6 (e) genes in mice liver (n = 6, mean ± SEM). Note: * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the model group.
Figure 8
Figure 8
(A) Venn diagram of OTUs sequence of stool sample. (B) Relative abundance of species at the bacteria Phylum level. (C) The relative abundance statistics of the largest species in each group after administration at the bacteria Phylum level. (D) The effect of GOS on the relative abundance ratio of Firmicutes and Bacteroides. (E) Heat map of relative abundance of different metabolites in each group at the bacteria Phylum level. (F) Relative abundance of species at the bacteria genus level. (G) The relative abundance statistics of the largest species in each group after administration at the bacteria genus level. Note: * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the model group (n = 4–5, mean ± SEM).
Figure 9
Figure 9
(A) Comparison of differences between groups of alpha diversity index. (B) Dimensionality reduction analysis results of beta diversity of mice in each group.
Figure 10
Figure 10
Species difference analysis diagram between t-test groups: (A) The control group vs the model group (n = 5), (B) the model group vs the GOS group (n = 5). (C) Histogram of LDA value distribution (n = 5), (D) LEfSe analysis evolutionary branch diagram (n = 5).
Figure 11
Figure 11
(A) Changes of SCFAs in the cecum content of mice in each group. Note: * p < 0.05, ** p < 0.01 vs. the model group; # p < 0.05, ## p < 0.01, ### p < 0.001 vs. the control group (n = 4–5, mean ± SEM). (B) Heat map of Spearman correlation at the phylum level. The strength of the color represents the degree of association. The heatmap shows the Spearman correlation between different microorganisms and different metabolites. The abscissa represents metabolites, the ordinate represents microorganisms, * represents a p value of < 0.05 in the correlation coefficient significance test, and ** represents a p value < 0.01. The abundance data of microorganisms and metabolites were standardized using Z scores.
Figure 12
Figure 12
(A) (a) Cell survival rates under different GOS concentrations (n = 6, mean ± SEM). ALT (b) and AST (c) contents in cell culture medium, intracellular TC (d) and TG (e) contents in each group after administration (n = 6, mean ± SEM). Effects of GOS on the expression of FAS (f), SREBP-1c (g), ACC1 (h), PPARα (i), SCD1 (j) PPARγ1 (k), PPARγ2, (l) IL-1β (m), TNF-α (n), and IL-6 (o) genes in each group (n = 6, mean ± SEM). Note: * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the FFA group. (B) Oil red O staining of cells in each group (400×).
Figure 13
Figure 13
The mechanism of GOS improving liver lipid accumulation in mice. Light green arrows indicate downregulation, green arrows indicates decrease, yellow and red arrows indicate an increasing effect.
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