Department of Pharmacology, Ufuk University School of Medicine, Ankara, Turkey.
Int J Gen Med. 2011;4:493-9. doi: 10.2147/IJGM.S18175. Epub 2011 Jun 24.
Ossabaw swine have a "thrifty genotype" and consumption of excess calories induces many classical components of the metabolic syndrome, including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and hypertension. Earlier studies indicate that the metabolic syndrome is associated with diminished cardiac function; however, to what degree this impairment is associated with alterations in myocardial β(1)- and β(2)-adrenoceptor (AR) expression has not been fully elucidated. Accordingly, the present study was designed to investigate the effects of the metabolic syndrome on cardiac β(1)- and β(2)-AR expression. Studies were conducted on left ventricular tissue samples obtained from control lean and chronically (50 weeks) high-fat-fed obese animals. Chronic feeding significantly increased fasting plasma insulin, total cholesterol, triglycerides, blood glucose, systolic and diastolic blood pressure, and heart rate. Real-time polymerase chain reaction revealed no significant alterations in cardiac β(1)- and β(2)-AR mRNA expression. In contrast, Western blot analysis revealed a significant decrease in ventricular β(1)- and β(2)-AR protein expression. This is the first report in a novel large animal model that induction of metabolic syndrome is accompanied by a significant reduction in cardiac β(1)- and β(2)-AR protein expression that could contribute to impaired cardiac function.
奥萨索猪具有“节俭基因型”,摄入过量卡路里会导致许多代谢综合征的经典成分,包括肥胖、胰岛素抵抗、葡萄糖耐量受损、血脂异常、高瘦素血症和高血压。早期研究表明,代谢综合征与心脏功能减退有关;然而,这种损害与心肌β(1)-和β(2)-肾上腺素能受体 (AR) 表达的改变有多大关系尚未完全阐明。因此,本研究旨在研究代谢综合征对心脏β(1)-和β(2)-AR 表达的影响。研究对象为取自对照瘦型和慢性(50 周)高脂肪喂养肥胖动物的左心室组织样本。慢性喂养显著增加了空腹胰岛素、总胆固醇、甘油三酯、血糖、收缩压和舒张压以及心率。实时聚合酶链反应显示心脏β(1)-和β(2)-AR mRNA 表达没有明显变化。相比之下,Western blot 分析显示心室β(1)-和β(2)-AR 蛋白表达显著降低。这是在新型大型动物模型中首次报道,代谢综合征的诱导伴随着心脏β(1)-和β(2)-AR 蛋白表达的显著减少,这可能导致心脏功能受损。