Abstract 8795: Cardiac Cachexia is Associated with Abnormal Liver Metabolism and Pro-Inflammatory Responses in a Rat Model of Heart Failure

Introduction: Cachexia, namely body wasting, is a common complication in heart failure (HF). Although neurohumoral and immune abnormalities are associated with the condition, the mechanism by which the imbalance of catabolism and anabolism occurs is not known. Hypothesis: We assessed the hypothesis that the liver is important in the pathogenesis of cardiac cachexia, since the liver plays a critical role in systemic metabolic regulation. Methods: We analyzed markers of cachexia in Dahl salt-sensitive rats fed a high salt diet which develop hypertension and, subsequently, HF. Dahl rats fed a low salt diet were used as a control. Glucose uptake of the liver was estimated using 18 F-deoxyglucose ( 18 FDG). The amount of metabolites in glycolysis and the Krebs cycle was measured employing metabolome analysis. Results and Conclusion: The body weight of HF rats was decreased compared with control rats (354±9 vs. 425±13 g, n=6, p<0.05). Food intake was reduced compared with controls by 29% (p<0.05). Blood sugar and insulin levels were decreased by 34 and 54%, respectively (p<0.05). Blood retinol binding protein (RBP), a hepatic protein, was decreased by 53% (p<0.05). The blood levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased. These results indicate that Dahl rats serve as a model of cardiac cachexia. Despite the apparent fasting condition, blood free fatty acid levels were decreased by 53% (p<0.05) and triglyceride (TG) levels were increased 2.0-fold (p<0.05). Next, we analyzed the livers of HF rats. 18 FDG uptake was increased 1.7-fold (p<0.05). The concentrations of some metabolites in the glycolytic pathway increased, and those in the Krebs cycle decreased. Gene expression related to lipogenesis increased and the TG content of the liver increased 1.8-fold (p<0.05). Gene expressions of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2, key enzymes in lipogenesis, increased 3.1- and 1.9-fold, respectively (p<0.05). The protein levels of SREBP-1c and SREBP-2 also increased. The gene and protein expressions of TNF-α and IL-1β increased in the liver. In conclusion, cardiac cachexia was associated with abnormal lipogenesis and proinflammatory responses in the liver, which might act as a maladaptive response in HF.