Matsuura Natsumi, Asano Chiharu, Nagasawa Kai, Ito Shogo, Sano Yusuke, Minagawa Yuji, Yamada Yuichiro, Hattori Takuya, Watanabe Shogo, Murohara Toyoaki, Nagata Kohzo
Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan.
Int J Cardiol. 2015 Jan 20;179:360-9. doi: 10.1016/j.ijcard.2014.11.099. Epub 2014 Nov 13.
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.
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.
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.
吡格列酮是一种噻唑烷二酮类药物，具有胰岛素增敏作用。我们最近将通过 Dahl 盐敏感大鼠与 Zucker 大鼠杂交获得的 DahlS.Z-Lepr(fa)/Lepr(fa)（DS/肥胖）大鼠鉴定为一种新的代谢综合征动物模型。我们现在研究了吡格列酮对该模型中心脏和脂肪组织病理学的影响。
DS/肥胖大鼠在 9 至 13 周龄时接受吡格列酮（每天 2.5 mg/kg，口服）治疗。年龄匹配的纯合瘦型（DahlS.Z-Lepr(+)/Lepr(+)，或 DS/瘦）同窝大鼠作为对照。吡格列酮增加了 DS/肥胖大鼠的体重和食物摄入量。它还改善了 DS/肥胖大鼠的左心室（LV）肥厚、纤维化和舒张功能障碍，减轻了心脏氧化应激和炎症，且未降低血压，但对 DS/瘦大鼠的这些参数没有影响。此外，吡格列酮增加了 DS/肥胖大鼠的内脏和皮下脂肪量，但减轻了内脏脂肪组织中的脂肪细胞肥大和炎症。此外，吡格列酮增加了血清脂联素浓度，诱导了心脏中 AMP 活化蛋白激酶（AMPK）的激活，并改善了 DS/肥胖大鼠的葡萄糖不耐受和胰岛素抵抗。
用吡格列酮治疗 DS/肥胖大鼠加剧了肥胖，但减轻了左心室肥厚、纤维化和舒张功能障碍，后一种作用可能与脂联素分泌受刺激导致心脏 AMPK信号激活有关。
