Natsumi Matsuura1, Chiharu Asano2, Kai Nagasawa1, Shogo Ito1, Yusuke Sano1, Yuji Minagawa2, Yuichiro Yamada1, Takuya Hattori1, Shogo Watanabe1, Toyoaki Murohara3, Kohzo Nagata4. 1. Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan. 2. Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan. 3. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 4. Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: nagata@met.nagoya-u.ac.jp.
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. 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.
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. METHODS AND RESULTS: DS/obeserats 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/obeserats. 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/obeserats, 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/obeserats. 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/obeserats. CONCLUSIONS: Treatment of DS/obeserats 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: Kasi C McPherson; Corbin A Shields; Bibek Poudel; Brianca Fizer; Alyssa Pennington; Ashley Szabo-Johnson; Willie L Thompson; Denise C Cornelius; Jan M Williams Journal: Am J Physiol Renal Physiol Date: 2018-12-12
Authors: Arnica Behringer; Manuela Trappiel; Eva Maria Berghausen; Henrik Ten Freyhaus; Ernst Wellnhofer; Margarete Odenthal; Florian Blaschke; Fikret Er; Natig Gassanov; Stephan Rosenkranz; Stephan Baldus; Kai Kappert; Evren Caglayan Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2016-01-07 Impact factor: 3.000
Authors: K Nagasawa; N Matsuura; Y Takeshita; S Ito; Y Sano; Y Yamada; A Uchinaka; T Murohara; K Nagata Journal: Nutr Diabetes Date: 2016-04-25 Impact factor: 5.097