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Betaine Protects Against High-Fat-Diet-Induced Liver Injury by Inhibition of High-Mobility Group Box 1 and Toll-Like Receptor 4 Expression in Rats

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Abstract

Background and Objectives

Previous studies have shown that betaine prevents alcohol-induced liver injury and improves liver function. The purpose of this study was to investigate the hepatoprotective effects of betaine on nonalcoholic fatty liver disease (NAFLD) and to observe changes of HMGB1/TLR4 signaling.

Methods

Thirty rats were randomly divided into control, model, and betaine groups. The rats in the model and betaine groups were fed a high-fat diet for 12 weeks to induce an animal model of NAFLD. The rats in the betaine group were then intragastrically administered betaine solution at a dose of 400 mg/kg per day for four weeks. Liver histology was examined. Serum levels of ALT, AST, TC, TG, HDL-C, LDL-C, FFA, HMGB1, NF-κB, TLR4, and tHcy were determined and intrahepatic TC, TG, and Hcy levels were assayed. mRNA expression and protein levels of HMGB1, NF-κB, and TLR4 in liver tissue were also determined.

Results

Compared with the control group, rats in the model group developed severe liver injury, accompanied by significant increases in serum levels of ALT, AST, TC, TG, LDL-C, FFA, HMGB1, NF-κB, and TLR4, intrahepatic TC, TG, and Hcy content, histological scores for steatosis, inflammation, and necrosis, and mRNA expression and protein levels of HMGB1, NF-κB, and TLR4, and a significant decrease in serum HDL-C (P < 0.05). Compared with the model group, all these indicators were significantly improved by administration of betaine (P < 0.05).

Conclusions

Betaine effectively protects against high-fat-diet-induced NAFLD and improves liver function; the mechanism is probably related to inhibition of HMGB1/TLR4 signaling pathways.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

ALT:

Serum alanine transaminase

AST:

Aspartate transaminase

TC:

Total cholesterol

TG:

Triglyceride

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

FFA:

Free fatty acid

HMGB1:

High-mobility group box 1

NF-κB:

Nuclear factor-κB

TLR4:

Toll-like receptor 4

tHcy:

Total homocysteine

Hcy:

Homocysteine

RT-PCR:

Reverse transcriptase polymerase chain reaction

WG:

Weight gain

LI:

Liver index

LPS:

Lipopolysaccharide

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Acknowledgments

This study was supported in part by a grant from the Natural Science Foundation of Hubei province (no. 2011CDB494).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jie Fang Road, Wuchang District, Wuhan, 430060, People’s Republic of China

    Wei Zhang, Lu-wen Wang, Li-kun Wang, Xun Li & Zuo-jiong Gong

  2. Pharmaceutical Department, Renmin Hospital of Wuhan University, 238 Jie Fang Road, Wuchang District, Wuhan, 430060, People’s Republic of China

    Hong Zhang, Li-Ping Luo & Jin-Chun Song

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  1. Wei Zhang
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Correspondence to Zuo-jiong Gong.

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Zhang, W., Wang, Lw., Wang, Lk. et al. Betaine Protects Against High-Fat-Diet-Induced Liver Injury by Inhibition of High-Mobility Group Box 1 and Toll-Like Receptor 4 Expression in Rats. Dig Dis Sci 58, 3198–3206 (2013). https://doi.org/10.1007/s10620-013-2775-x

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  • DOI: https://doi.org/10.1007/s10620-013-2775-x

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