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Cardiac Complications associated with the Metabolic Syndrome


Lene Nygaard Axelsen


Heart disease is prevalent in patients with the metabolic syndrome and several lines ofevidence indicate that alterations in cardiac metabolism play a critical role in thedevelopment of cardiac dysfunction in these patients. Therefore, modulation ofcardiac metabolism is increasingly recognized as a potential approach for treatment ofheart diseases in patients with the metabolic syndrome.Initially, high fructose and fat fed rats (FFFRs) and high cholesterol and fructose(HCF) fed rats, were evaluated for their usefulness as diet-induced animal models ofthe metabolic syndrome and associated cardiac complications. FFFRs graduallydeveloped several metabolic changes, which resulted in a phenotype of metabolicsyndrome similar to that found in humans. The aerobic cardiac function remainedunchanged in FFFRs during 48 weeks of feeding, but they were much more sensitiveto cardiac ischemia-reperfusion injury. HCF feeding of rats led to an elevated serumcholesterol level and a decreased HDL level, but no change in body weight or glucosetolerance could be detected. Furthermore, we did not identify any changes in cardiacfunction following 15 weeks on a HCF diet, which is in contrast to findings reportedby another group. Our data demonstrate that FFFRs is a useful animal model forfuture studies of the metabolic syndrome and its cardiac complications. Theincongruence between our HCF rat study and the other study mentioned aboveemphasize that studies on diet-induced animal models of the metabolic syndromemust be intercepted with care since genetic and/or environmental factors mayinterfere with the outcome of the study.Despite a significantly decreased glycolysis and glucose oxidation in isolated heartsfrom insulin-resistant JCR:LA rats, we found no significant effect of the GLP-1receptor agonist ZP131 on cardiac glucose metabolism during unstressed conditions.The glucagon-GLP-1 dual-agonist ZP2495 had similar inotropic effects as glucagon,but in contrast to glucagon, ZP2495 did not compromise the energetic state of insulinresistanthearts. Potentially this effect of ZP2495 could lead to beneficial effects onsurvival rates compared to other inotropic compounds currently used to treat acutedecompensated heart failure or cardiogenic shock. However, the mechanismswhereby ZP2495 improve the energetic state of the hearts remain to be determined.