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, 10 (10), 10261-10268
eCollection

Glycine Protects Against Non-Alcoholic Hepatitis by Downregulation of the TLR4 Signaling Pathway

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Glycine Protects Against Non-Alcoholic Hepatitis by Downregulation of the TLR4 Signaling Pathway

Xi Yang et al. Int J Clin Exp Pathol.

Abstract

Objective: To evaluate the effect of glycine on regulation of the hepatic toll-like receptor 4 (TLR4) signaling pathway by metabolic endotoxemia in a rat model of non-alcoholic steatohepatitis (NASH).

Methods: The NASH rat model was generated by feeding the animals a high-sucrose, high-fat for diet for 12 weeks. We then measured alterations in levels of LPS, TNFα, IL-6, ALT, TG in plasma, and TNFα, and IL-6 in liver. We performed hematoxylin and eosin (HE) staining and immunohistochemical staining to document pathological changes. Expression of TLR4 and IRS-1 in liver was measured by Western Blot and RT-PCR.

Results: Compared with control animals, levels of LPS, TNFα, IL-6 in plasma and the levels of TNFα, IL-6 in liver tissues gradually increased. Pathological changes and expression of TLR4 in liver were significantly increased compared with control. mRNA and protein levels of TLR4 and IRS-1 in livers were also upregulated. With concomitant treatment with glycine, endotoxin levels decreased, and TNFα and IL-6 levels in plasma and liver were significantly decreased compared to NASH rats. Pathological changes in liver and immunohistological expression of TLR4 in liver tissues were significantly improved compared to NASH rats. mRNA and protein levels of TLR4 were significantly downregulated while mRNA and protein levels of IRS-1 in liver were markedly upregulated. Progression of NASH appeared to be slowed or limited.

Conclusion: These data suggest that hepatic TLR4 signaling pathway is activated in the NASH rat, and oral glycine may reduce the risk of endotoxemia and inflammation of the liver.

Keywords: Glycine; intestinal endotoxin; non-alcoholic steatoheptitis; type 4 toll-like receptors.

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Effect of glycine treatment on LPS, biochemistry and systemic inflammation indices. Control group (C), high-fat/high-sugar group (H), high-fat/high-sugar + glycine group (H+G), glycine group (G). Data represented as means ± standard error (n=8). aP < 0.05 vs control group; bP < 0.05 vs HSHF group.
Figure 2
Figure 2
Effect of glycine treatment on liver pathology. Control group (C), high-fat/high-sugar group (H), high-fat/high-sugar + glycine group (H+G), glycine group (G).
Figure 3
Figure 3
Effect of glycine treatment on the expression of TLR4 by immunohistochemical staining. Control group (C), high-fat/high-sugar group (H), high-fat/high-sugar + glycine group (H+G), glycine group (G).
Figure 4
Figure 4
Effect of glycine treatment on the mRNA expression of TLR4 and IRS-1 by PCR. Control group (C), high-fat/high-sugar group (H), high-fat/high-sugar + glycine group (H+G), glycine group (G). Data represented as mean ± standard error (n=8). aP < 0.05 vs control group; bP < 0.05 vs HSHF group.
Figure 5
Figure 5
Effect of glycine treatment on the protein expression of TLR4 and IRS-1 by Western blot. Control group (C), high-fat/high-sugar group (H), high-fat/high-sugar + glycine group (H+G), glycine group (G). Data represented as means ± standard error (n=8). aP < 0.05 vs standard control group; bP < 0.05 vs HSHF group.

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