TY - JOUR
T1 - Effects of pioglitazone on cardiac and adipose tissue pathology in rats with metabolic syndrome
AU - Matsuura, Natsumi
AU - Asano, Chiharu
AU - Nagasawa, Kai
AU - Ito, Shogo
AU - Sano, Yusuke
AU - Minagawa, Yuji
AU - Yamada, Yuichiro
AU - Hattori, Takuya
AU - Watanabe, Shogo
AU - Murohara, Toyoaki
AU - Nagata, Kohzo
N1 - Funding Information:
Acknowledgment of grant support: This study was supported by unrestricted research grants from Kyowa Hakko Kirin Co. Ltd. (Tokyo, Japan) , Ajinomoto Pharmaceuticals Co., Ltd. (Tokyo, Japan) , Astellas Pharma Inc. (Tokyo, Japan) , Mochida Pharmaceutical Co., Ltd. (Tokyo, Japan) , Mitsubishi Tanabe Pharma Corporation (Osaka, Japan) , Takeda Pharmaceutical Company Limited (Osaka, Japan) , Daiichi-Sankyo Company, Limited (Tokyo, Japan) and Dr. Nagata (Nagoya University) as well as by Management Expenses Grants from the Japanese government to Nagoya University.
Publisher Copyright:
© 2014 Elsevier Ireland Ltd. All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/1/20
Y1 - 2015/1/20
N2 - 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.
AB - 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.
KW - Adipose tissue
KW - Cardiac remodeling
KW - Glucose metabolism
KW - Inflammation
KW - Metabolic syndrome
KW - Thiazolidinedione
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U2 - 10.1016/j.ijcard.2014.11.099
DO - 10.1016/j.ijcard.2014.11.099
M3 - Article
C2 - 25464487
AN - SCOPUS:84920643340
SN - 0167-5273
VL - 179
SP - 360
EP - 369
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -
