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.

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.

• Authors: Natsumi Matsuura, Chiharu Asano, Kai Nagasawa, Shogo Ito, Yusuke Sano, Yuji Minagawa, Yuichiro Yamada, Takuya Hattori, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata
• Journal: International journal of cardiology (Int J Cardiol) Vol. 179 Pg. 360-9 (Jan 20 2015) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 25464487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Thiazolidinediones
• Pioglitazone

Topics

• Adipocytes (drug effects, metabolism, pathology)
• Adipose Tissue (drug effects, metabolism, pathology)
• Animals
• Male
• Metabolic Syndrome (drug therapy, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Pioglitazone
• Rats
• Rats, Inbred Dahl
• Rats, Zucker
• Thiazolidinediones (pharmacology, therapeutic use)
• Treatment Outcome