Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia.
J Cardiovasc Pharmacol. 2011 May;57(5):611-24. doi: 10.1097/FJC.0b013e31821b1379.
The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.
代谢综合征的患病率包括中心性肥胖、胰岛素抵抗、葡萄糖耐量受损、高血压和血脂异常正在增加。开发代谢综合征的充分治疗方法需要一种模拟人类疾病状态的动物模型。因此,我们描述了雄性 Wistar 大鼠(8-9 周龄)在高碳水化合物、高脂肪饮食中的代谢、心血管、肝脏、肾脏和胰腺变化,该饮食包括炼乳(39.5%)、牛脂(20%)和果糖(17.5%),同时在饮水中含有 25%的果糖;对照组大鼠喂食玉米淀粉饮食。在这种饮食 16 周期间,大鼠体重、能量摄入、腹部脂肪沉积和腹围逐渐增加,同时出现葡萄糖耐量受损、血脂异常、高胰岛素血症和血浆瘦素和丙二醛浓度增加。心血管迹象包括收缩压升高和内皮功能障碍,同时伴有炎症、纤维化、肥大、左心室僵硬和复极化延迟。肝脏表现出湿重增加、脂肪沉积、炎症和纤维化,同时血浆肝功能酶活性增加。肾脏出现炎症和纤维化,而胰腺出现胰岛增大。与其他糖尿病和肥胖模型相比,这种饮食诱导的模型更能模拟人类代谢综合征观察到的变化。