title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jie Fang Road, Wuchang District, Wuhan, 430060, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lu-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Luo
authors.forename: Jin-Chun
authors.initials: JC
authors.lastname: Song
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects*; D005234:Fatty Liver / Q000517:prevention & control; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D024742:HMG-Box Domains / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D016207:Cytokines; D004041:Dietary Fats; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D001622:Betaine