Irisin Directly Affects Cardiac Glucose Oxidation and Contractile Function

Background: Irisin is a peptide hormone liberated by skeletal muscle which may regulate thermogenesis in adipose tissue. Recent data point to a correlation between increased irisin levels and adverse cardiovascular events in patients with coronary artery disease and in those suffering from acute heart failure. However, it is unclear whether and how irisin affects the heart. We assessed the direct effects of irisin on cardiac substrate utilization and function.

Methods and Results: Hearts of Sprague-Dawley rats (300–350 g) were perfused in the working mode with 5 mM glucose and 0.4 mM oleate as substrates for 60 minute. At 30 minute, irisin was added at 1.5 nM or 15 nM. We measured changes in fatty acid and glucose oxidation as well as cardiac function. Irisin showed no effect on cardiac fatty acid oxidation. In contrast, the addition of irisin reduced glucose oxidation at both 1.5 nM (−54.3 ± 8%) and 15 nM (−41.2 ± 8.7%). Furthermore, irisin significantly decreased cardiac power at 1.5 nM (€14.6 ± 4.1%) and 15 nM (−29.8 ± 4.2%).

Conclusions: Irisin has no direct effect on cardiac fatty acid utilization but depresses glucose oxidation. Furthermore, irisin decreases cardiac power. This contractile dysfunction may be attributed to impaired cardiac energetics. From a clinical perspective, the results imply that high irisin levels in patients undergoing cardiac surgery may affect outcome by modulating cardiac glucose metabolism and contractile function. The role of irisin in the heart requires further investigations.