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. 2023 Oct 3;28(19):6918.
doi: 10.3390/molecules28196918.

Glucosamine Improves Non-Alcoholic Fatty Liver Disease Induced by High-Fat and High-Sugar Diet through Regulating Intestinal Barrier Function, Liver Inflammation, and Lipid Metabolism

Feng Li  1   2 , Zhengyan Zhang  1   2 , Yan Bai  3 , Qishi Che  4 , Hua Cao  5 , Jiao Guo  2 , Zhengquan Su  1
Affiliations

Glucosamine Improves Non-Alcoholic Fatty Liver Disease Induced by High-Fat and High-Sugar Diet through Regulating Intestinal Barrier Function, Liver Inflammation, and Lipid Metabolism

Feng Li et al. Molecules. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a liver disease syndrome. The prevalence of NAFLD has continued to increase globally, and NAFLD has become a worldwide public health problem. Glucosamine (GLC) is an amino monosaccharide derivative of glucose. GLC has been proven to not only be effective in anti-inflammation applications, but also to modulate the gut microbiota effectively. Therefore, in this study, the therapeutic effect of GLC in the NAFLD context and the mechanisms underlying these effects were explored. Specifically, an NAFLD model was established by feeding mice a high-fat and high-sugar diet (HFHSD), and the HFHSD-fed NAFLD mice were treated with GLC. First, we investigated the effect of treating NAFLD mice with GLC by analyzing serum- and liver-related indicator levels. We found that GLC attenuated insulin resistance and inflammation, increased antioxidant function, and attenuated serum and liver lipid metabolism in the mice. Then, we investigated the mechanism underlying liver lipid metabolism, inflammation, and intestinal barrier function in these mice. We found that GLC can improve liver lipid metabolism and relieve insulin resistance and oxidative stress levels. In addition, GLC treatment increased intestinal barrier function, reduced LPS translocation, and reduced liver inflammation by inhibiting the activation of the LPS/TLR4/NF-κB pathway, thereby effectively ameliorating liver lesions in NAFLD mice.

Keywords: glucosamine; inflammation; intestinal barrier; liver lipid metabolism; non-alcoholic fatty liver disease.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Changes in food intake level, body weight, serum glucose, and insulin levels. (A) The total food intake level, (B) weekly weight change, (C) weight gain, (D) fasting blood glucose level, (E) serum glucose curve, (F) area under the glucose curve, and (G) serum insulin level. The data are presented as the mean ± SEM (n = 8). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the model group.
Figure 2
Figure 2
GLC can improve serum lipid metabolism in HFHSD-fed mice. (A) Serum TG level, (B) serum TC level, (C) serum LDL-C level, (D) serum HDL-C level, and (E) serum FFA level. The data are presented as the mean ± SEM (n = 8). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the model group.
Figure 3
Figure 3
GLC improves serum transaminase levels as well as inflammation and oxidative function in NAFLD mice. (A) Serum AST level, (B) serum ALT level, (C) serum IL-6 level, (D) serum TNF-α level, (E) serum IL-10 level, (F) serum CAT level, and (G) serum T-AOC in each group of mice after the treatment. The data are presented as the mean ± SEM (n = 8). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the model group.
Figure 4
Figure 4
GLC improves liver lipid accumulation and oxidative function in NAFLD mice. (A) The overall morphology of the liver, (B) H&E stained tissue, (C) oil red O stained tissue, (D) liver TC level, (E) liver TG level, (F) liver LDL-C level, (G) liver HDL-C level, (H) liver SOD level, (I) liver MDA level, (J) liver CAT level, and (K) liver GSH level. The data are presented as the mean ± SEM (n = 6). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the model group.
Figure 5
Figure 5
The effect of GLC on liver lipid metabolism. After GLC treatment, the expression of (A) SREBP-1, (B) PPARγ, and (C) ACC decreased and the expression of (D) CPT1 increased. The data are presented as the mean ± SEM (n = 6). * p < 0.05, ** p < 0.01 compared to the model group.
Figure 6
Figure 6
The effect of GLC on inflammation. (A) IL-6, (B) IL-1β, (C) TNF-α gene expression levels (n = 6), (D) serum LPS level, (E) the expression of the p-NF-κB and NF-κB proteins, (F) TLR4, CD14, and MYD88 protein levels (n = 4). The data are presented as the mean ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the model group.
Figure 7
Figure 7
The effect of GLC on intestinal barrier function. (A) H&E staining of sections of ileum (200×) and (B) colon (200×). (C) The protein expression levels of ileum ZO-1, (D) colon ZO-1, (E) ileum Occludin, (F) colon Occludin, (G) ileum Claudin-1, and (H) colon Claudin-1. The data are presented as the mean ± SEM (n = 3). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the model group.
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