title: Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.
abstract: BACKGROUND
  We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress.
  
  
  METHODS
  Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels.
  
  
  RESULTS
  After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY.
  
  
  CONCLUSIONS
  Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress.
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Kanno
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ikuta
authors.affiliation: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sugiyama
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Kishikawa
authors.affiliation: Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. stazuma@hiroshima-u.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tazuma
mesh_terms: D000818:Animals; D002794:Choline / Q000494:pharmacology*; D004032:Diet; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D008082:Lipotropic Agents / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000178:diet therapy / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D008082:Lipotropic Agents; D017392:Thiobarbituric Acid Reactive Substances; D002794:Choline
keywords: Glutathione peroxidase; Liver fibrosis; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Oxidative stress; Superoxide dismutase