title: Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is a common health problem and includes a spectrum of hepatic steatosis, steatohepatitis and fibrosis. The renin-angiotensin system (RAS) plays a vital role in blood pressure regulation and appears to promote hepatic fibrogenesis. We hypothesized that increased RAS activity causes NAFLD due to increased hepatic oxidative stress.
  
  
  METHODS
  We employed the transgenic TG(mRen2)27(Ren2) hypertensive rat, harboring the mouse renin gene with elevated tissue Angiotensin II (Ang II).
  
  
  RESULTS
  Compared with normotensive Sprague-Dawley (SD) control rats, Ren2 developed significant hepatic steatosis by 9 weeks of age that progressed to marked steatohepatitis and fibrosis by 12 weeks. These changes were associated with increased levels of hepatic reactive oxygen species (ROS) and lipid peroxidation. Accordingly, 9-week-old Ren2 rats were treated for 3 weeks with valsartan, an angiotensin type 1 receptor blocker, or tempol, a superoxide dismutase/catalase mimetic. Hepatic indices for oxidative stress, steatosis, inflammation and fibrosis were markedly attenuated by both valsartan and tempol treatment.
  
  
  CONCLUSIONS
  This study suggests that Ang II causes development and progression of NAFLD in the transgenic Ren2 rat model by increasing hepatic ROS. Our findings also support a potential role of RAS in prevention and treatment of NAFLD.
authors.affiliation: Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wei
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Clark
authors.forename: E Matthew
authors.initials: EM
authors.lastname: Morris
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.forename: Grace M E
authors.initials: GM
authors.lastname: Uptergrove
authors.forename: Adam T
authors.initials: AT
authors.lastname: Whaley-Connell
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism* / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013113:Spin Labels; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; C473112:Ren2 protein, mouse; D013113:Spin Labels; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D012083:Renin; D014633:Valine; C001803:tempol