A1 adenosine receptor activation increases adipocyte leptin secretion

A1 adenosine receptors (AIARs) are heavily expressed in adipocytes and infl uence fat cell metabolism. Because increasing evidence suggests a role for leptin in mediating appetite and fat cell metabolism, we tested whether A1A Rs regulate leptin production. Rats were treated with the A1AR agonist N-6- cyclopentyladenosine (CPA), and changes in circulating levels of leptin and leptin gene expression were examined. Serum leptin levels rose 2- to 10-fo ld, with peak increases seen 8-16 h after injection of CPA (P < 0.05). In c ontrast, CPA did not alter steady state levels of adipose tissue leptin mRN A. To assess the influence of endogenous adenosine on circulating leptin le vels, rats were also injected with dipyridamole (DPY), an adenosine reuptak e blocker. DPY induced 80% increases in serum levels at 8 h alter injection s (P < 0.05). Supporting the idea that stimulation of leptin production isA 1AR mediated, pretreatment with the A1AR antagonist 8-cyclopentyl-1,3-dipro pylxanthine completely blocked increases in leptin levels after DPY treatme nt. To complement in vivo studies, the effect of A1AR activation on leptin secretion was also studied in epididymal fat pad cultures. In cultures, CPA treatment increased leptin secretion by 37% (P < 0.05). Collectively, thes e data show that the adenosinergic system can increase leptin secretion by directly activating A1ARs in fat tissue.