title: α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats.
abstract: BACKGROUND
  Insulin resistance, oxidative stress, inflammation and innate immune system activation contribute to the development of non-alcoholic fatty liver disease (NAFLD) through steatosis and inflammation in the liver. The powerful antioxidant α-lipoic acid (ALA) has been shown to improve insulin sensitivity and suppress inflammatory responses. This study explores how ALA administration protects against NAFLD.
  
  
  METHODS
  Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into two groups (treated with 200 mg/kg/day of ALA or untreated) at 12 weeks of age and sacrificed at 28 weeks of age.
  
  
  RESULTS
  Serum levels of insulin, free fatty acids, total cholesterol, triglyceride, leptin, IL-6 and blood glucose were decreased in ALA-treated rats. Serum adiponectin levels were higher in ALA-treated rats. ALA treatment decreased the expression of sterol regulatory element binding protein-1 and acetyl CoA carboxylase, and increased glucose transporter-4 expression in the livers of OLETF rats. Expression of the antioxidant enzymes heme oxygenase-1 and Cu/Zn-superoxide dismutase was increased in the livers of ALA-treated rats. The lipid peroxidation marker 4-hydroxynonenal was decreased in the liver of ALA-treated rats. Proteins associated with innate immune activation (Toll-like receptor-4 and high-mobility group protein box-1) and inflammatory markers (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and cyclooxygenase-2) were decreased in the livers of ALA-treated rats.
  
  
  CONCLUSIONS
  Chronic ALA supplementation prevents NAFLD through multiple mechanisms by reducing steatosis, oxidative stress, immune activation and inflammation in the liver.
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
authors.forename: Tae Sik
authors.initials: TS
authors.lastname: Jung
authors.forename: Soo Kyoung
authors.initials: SK
authors.lastname: Kim
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Shin
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.forename: Jong Ryeal
authors.initials: JR
authors.lastname: Hahm
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D005234:Fatty Liver / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D020334:Rats, Inbred OLETF; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D052242:Adiponectin; D000447:Aldehydes; D001391:Azo Compounds; D001786:Blood Glucose; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D051780:Sterol Regulatory Element Binding Protein 1; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008063:Thioctic Acid; D002784:Cholesterol; D051546:Cyclooxygenase 2; D000103:Acetyl-CoA Carboxylase; C011049:oil red O; C027576:4-hydroxy-2-nonenal