title: Effects of pioglitazone on cardiac and adipose tissue pathology in rats with metabolic syndrome.
abstract: BACKGROUND
  Pioglitazone is a thiazolidinedione drug that acts as an insulin sensitizer. We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. We have now investigated the effects of pioglitazone on cardiac and adipose tissue pathology in this model.
  
  
  RESULTS
  DS/obese rats were treated with pioglitazone (2.5 mg/kg per day, per os) from 9 to 13 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean) littermates served as controls. Pioglitazone increased body weight and food intake in DS/obese rats. It also ameliorated left ventricular (LV) hypertrophy, fibrosis, and diastolic dysfunction as well as attenuated cardiac oxidative stress and inflammation, without lowering blood pressure, in DS/obese rats, but it had no effect on these parameters in DS/lean rats. In addition, pioglitazone increased visceral and subcutaneous fat mass but alleviated adipocyte hypertrophy and inflammation in visceral adipose tissue in DS/obese rats. Furthermore, pioglitazone increased the serum concentration of adiponectin, induced activation of AMP-activated protein kinase (AMPK) in the heart, as well as ameliorated glucose intolerance and insulin resistance in DS/obese rats.
  
  
  CONCLUSIONS
  Treatment of DS/obese rats with pioglitazone exacerbated obesity but attenuated LV hypertrophy, fibrosis, and diastolic dysfunction, with these latter effects being associated with the activation of cardiac AMPK signaling likely as a result of the stimulation of adiponectin secretion.
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Matsuura
authors.affiliation: Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Asano
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Nagasawa
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minagawa
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: nagata@met.nagoya-u.ac.jp.
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D000077205:Pioglitazone; D051381:Rats; D020303:Rats, Inbred Dahl; D011924:Rats, Zucker; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Adipose tissue; Cardiac remodeling; Glucose metabolism; Inflammation; Metabolic syndrome; Thiazolidinedione