EXPRESSION OF LEPTIN AND LEPTIN RECEPTOR ISOFORMS IN HUMAN
MYOCARDIUM: A ROLE IN CARDIAC FUNCTION AND THE PATHOPHYSIOLOGY OF CHF? G. Wiesner*, M. Esler and D. M. Kaye. Baker Medical Research Institute and Alfred Baker Medical
Unit, Alfred Hospital, Melbourne, Vic. Leptin is a hormone secreted largely by adipose cells
which acts centrally to regulate adiposity and energy balance. In addition, the presence of leptin
receptors in the heart suggests a direct role for leptin in cardiac
metabolism. Given these observations,
we sought to characterize leptin's involvement in cardiac metabolism, including
its effect on fuel (substrate) preference, and its potential role in the
pathophysiology of congestive heart failure (CHF) which is a known state of
energy imbalance. Transcardiac leptin flux to plasma was measured in 20
healthy volunteers and 24 CHF patients.
Net positive transcardiac leptin overflow was present in CHF (154 ± 67
ng/min, P <0.02), but absent in healthy subjects. Neither systemic leptin levels nor the rate of cardiac leptin
secretion differed between normal weight and underweight patients with CHF.
Expression of the four known human leptin receptor isoforms and of the leptin
gene itself was assessed by RT-PCR in CHF (n=2) and control (n=1) myocardium. Consistent expression of leptin and all
receptor variants, including appreciable expression of the long signaling form,
was observed. Substrate uptake experiments performed with cultured rat
cardiomyoctes revealed that leptin increased fatty acid (palmitate) uptake, but
had no effect on glucose uptake. In conclusion, leptin mRNA is expressed in both healthy
and failing human myocardium, but leptin secretion is apparent only from the
failing heart. All of the known leptin
receptor isoforms are expressed in human myocardium. Leptin's role in the metabolism of the failing heart requires
further investigation, however in vitro results indicate that leptin may
stimulate fatty acid uptake in the heart.
