Cardiac ß-adrenoceptor expression is markedly depressed in Ossabaw swine model of cardiometabolic risk

Abstract

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.