Leptin - a cardioprotective hormone following CPB or an innocent bystander?

Leptin, the adipocyte-derived peptide encoded by the ob gene, promotes weight loss by reducing appetite and increasing energy expenditure. However, it has multiple other physiological functions, including regulation of neuroendocrine, reproductive, hemopoietic and metabolic pathways. Multiple studies suggest that leptin may be involved in the acute stress response, and that its interaction with the hypothalamic-pituitary-adrenal axis and inflammatory cytokines may be of clinical importance. A wealth of studies defined a close relationship between cardiovascular function and leptin. Leptin receptors as well as leptin mRNA have been identified in myocardial tissue, and it has been suggested that the hormone may have a cardioprotective effect. Several studies suggested that open heart surgery (OHS) and cardiopulmonary bypass (CPB), a well-recognized initiator of a systemic inflammatory response, is associated with acute changes in circulating leptin levels. CPB resulted in a bi-phasic pattern of change in leptin levels - an initial decrease followed by an increase in leptin levels that was sustained up to 24 hours postoperatively. Leptin levels were inversely correlated with IL-6, the main cytokine released after cardiac surgery. A negative correlation between cortisol and leptin levels was also observed. Administration of exogenous glucocorticoid affected the amplitude, but not the pattern, of plasma leptin levels following CPB. A more complicated post-operative course may be associated with lower leptin levels. Furthermore, there was a negative association between leptin levels and troponin levels following OHS with CPB, suggesting an association between myocardial injury and attenuation of leptin levels. In keeping with these findings, leptin deficiency is linked to worse outcomes in chronic ischemic injury. The apparent beneficial role of leptin in the recovery from CPB may be attributed to enhancement of the anti-inflammatory response, as well as to its OHS with CPB is still associated with significant morbidity and mortality, measurement of leptin levels may enhance risk stratification, and the modulation of leptin through current and future therapies could possibly contribute to reducing morbidity and mortality following cardiac surgery.