Abstract 558
Endcrinology I Poster Symposium, Saturday, 5/1
Leptin is a peptide hormone that exerts important effects on appetite and fat cell metabolism. Currently our understanding of the factors that regulate leptin secretion is at early stages. Because A1 adenosine receptors (A1AR) potently influence fat cell metabolism, we hypothesize that adenosine is an important regulator of leptin production. To test this hypothesis, rats were injected with the A1AR agonist N6-cyclopentyladenosine (CPA; i.p.) and changes in circulating levels of leptin and leptin gene expression examined. Results revealed that A1AR agonist treatment resulted in 20% increases in leptin mRNA levels 4 hours after treatment, and 2 to 10-fold increases in plasma leptin levels at 4-8 hours after injection. These effects were blocked by pretreating animals with the A1AR specific antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Next, we tested if endogenous adenosine regulates leptin production. Rats were treated with DPCPX or the adenosine reuptake blocker dipyridamole. No changes in circulating leptin levels were seen after DPCPX treatment, suggesting that basal levels of adenosine do not play a role in tonic leptin secretion. However, dipyridamole treatment resulted in 2.5-fold increases in plasma leptin levels, suggesting that increasing local adenosine levels triggers leptin secretion. Overall, these data strongly support the notion that adenosine acts through A1ARs to potently stimulate leptin secretion. We are currently unaware of any other humoral signals that so potently regulate leptin secretion in vivo.
