title: Pioglitazone upregulates hepatic angiotensin converting enzyme 2 expression in rats with steatohepatitis.
abstract: OBJECTIVE
  Angiotensin II, one component of renin-angiotensin system (RAS), is formed from Ang I by the catalysing of angiotensin converting enzyme (ACE). Angiotensin II plays an important role in the development of insulin resistance. ACE2, a homologue of ACE, couterregulate the actions of angiotensin II by facilitating its breakdown to angiotensin-(1-7). RAS has been implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH). Earlier demonstration that thiazolidinediones (TZDs) improve steatohepatitis promoted us to evaluate the change of hepatic ACE2 expression in rats with high fat diet (HFD)-induced NASH and the effects of TZDs on the hepatic ACE2 expression.
  
  
  METHODS
  Rats were divided into normal control group, high fat diet (HFD) group, and pioglitazone group. After 24 weeks of treatment with pioglitazone, a TZD, we evaluated changes in liver histology, insulin sensitivity, lipid metabolism, circulating RAS levels and hepatic ACE2 expression.
  
  
  RESULTS
  Compared with normal controls, the concentrations of serum lipid, aminotransaminase, glucose, insulin, ACE, angiotensin II, ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression were significantly higher in rats with HFD-induced NASH. Pioglitazone significantly reduced the concentrations of serum lipid, aminotransaminase, glucose, insulin, ACE, angiotensin II while markedly raised the concentrations of serum ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression.
  
  
  CONCLUSIONS
  Hepatic ACE2 expression markedly increased in rats with HFD-induced NASH and was further upregulated by pioglitazone. Hepatic ACE2 may be a new target of pioglitazone treatment for NASH.
authors.affiliation: Department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical University.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Nan
authors.initials: N
authors.lastname: Zou
authors.forename: Yi-Zhi
authors.initials: YZ
authors.lastname: Xu
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Hua-Mei
authors.initials: HM
authors.lastname: Zhou
authors.forename: Ke-Qiang
authors.initials: KQ
authors.lastname: Wan
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Xiao
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D045162:Thiazolidinediones; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D000077205:Pioglitazone