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. 2013 Nov;58(11):3198-206. doi: 10.1007/s10620-013-2775-x. Epub 2013 Jul 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betaine / pharmacology*
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dietary Fats / adverse effects*
  • Fatty Liver / prevention & control
  • Female
  • Gene Expression Regulation / physiology*
  • HMG-Box Domains / genetics
  • HMG-Box Domains / physiology*
  • Lipid Metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism
  • Non-alcoholic Fatty Liver Disease
  • Rats
  • Rats, Sprague-Dawley
  • Specific Pathogen-Free Organisms
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Weight Gain


  • Cytokines
  • Dietary Fats
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Betaine