title: Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats.
  
  
  METHODS
  Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression.
  
  
  RESULTS
  ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group.
  
  
  CONCLUSIONS
  Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology, Chongqing the Third Hospital, Chongqing 400014, China.
authors.forename: Yi-Zhi
authors.initials: YZ
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Yang
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D000077205:Pioglitazone; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D000077205:Pioglitazone