Effects of pioglitazone on cardiac and adipose tissue pathology in rats with metabolic syndrome

Natsumi Matsuura, Chiharu Asano, Kai Nagasawa, Shogo Ito, Yusuke Sano, Yuji Minagawa, Yuichiro Yamada, Takuya Hattori, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Background Pioglitazone is a thiazolidinedione drug that acts as an insulin sensitizer. We recently characterized DahlS.Z-Leprfa/Leprfa (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. Methods and 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.

Original languageEnglish
Pages (from-to)360-369
Number of pages10
JournalInternational Journal of Cardiology
Publication statusPublished - Jan 20 2015
Externally publishedYes


  • Adipose tissue
  • Cardiac remodeling
  • Glucose metabolism
  • Inflammation
  • Metabolic syndrome
  • Thiazolidinedione

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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