title: Spontaneously hypertensive rats develop pronounced hepatic steatosis induced by choline-deficient diet: Evidence for hypertension as a potential enhancer in non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  Patients with non-alcoholic steatohepatitis (NASH) frequently have many co-morbidities including essential hypertension, which is reported to increase vascular production of reactive oxygen species (ROS) and alter the hepatic anti-oxidant defense system. Since ROS play a role in the pathogenesis of NASH, it is hypothesized that hypertension modulates the hepatic oxidative status and influences the development of NASH. The aim of this study was to investigate the potential effects of hypertension on the progression of NASH.
  
  
  METHODS
  Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats as normotensive controls were fed choline-deficient (CD) diet for 5 weeks. Histological changes, messenger RNA (mRNA) expression and thiobarbituric acid reactive substances (TBARS) levels in the liver were assessed in each group.
  
  
  RESULTS
  Choline-deficient diet led to pronounced hepatic steatosis in SHR with an 8-fold increase of the hepatic triglyceride content, while there was no significant increase in WKY. These changes in SHR were associated with significant reduction in the expression of mRNA for peroxisome proliferator activated receptor α, acyl-CoA oxidase, microsomal triglyceride transfer protein, and apolipoprotein B100. Consistent with the significant reduction of hepatic superoxide dismutase activity and marked downregulation of the gene expression of hepatic antioxidant enzymes, the hepatic TBARS level and the plasma level of alanine aminotransferase were only increased in SHR on CD diet.
  
  
  CONCLUSIONS
  Spontaneously hypertensive rats receiving CD diet showed severe hepatic steatosis associated with reduction of hepatic anti-oxidant capacity, leading to increased hepatic oxidative stress and tissue damage. Accordingly, hypertension might have a potential effect on the progression of NASH.
authors.affiliation: Departments of General Internal Medicine             Anatomical Pathology             Pharmaceutical Services, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ikuta
authors.forename: Keishi
authors.initials: K
authors.lastname: Kanno
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Sosuke
authors.initials: S
authors.lastname: Matsuda
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Kishikawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujita
authors.forename: Susumu
authors.initials: S
authors.lastname: Tazuma