Stimulation of leptin release by arachidonic acid and prostaglandin E2 in adipose tissue from obese humans

Abstract

The purpose of this study was to examine the effect of arachidonic acid and its metabolites on leptin formation by explants of human adipose tissue over a 48-hour incubation in primary culture. We found that arachidonic acid or prostaglandin E2 (PGE2) stimulated leptin release by explants of subcutaneous adipose tissue from obese humans. The stimulatory effect of arachidonic acid on leptin formation was blocked by NS-398, a cyclooxygenase-2 (COX-2) inhibitor. There was appreciable release of PGE2 to the medium over 48 hours, and this was inhibited by 99% in the presence of 200 nmol/L dexamethasone or 5 [mu ]mol/L NS-398. The increase in PGE2 release correlated with induction of COX-2 activity during the 48-hour incubation. The increase in COX-2 activity was blocked by 200nmol/L dexamethasone. The level of leptin mRNA at 48 hours was reduced by 28% if PGE2 was added in the absence of dexamethasone, while in the presence of dexamethasone, the amount of leptin mRNA was enhanced by 156%. These data suggest that when upregulation of COX-2 is blocked by dexamethasone, exogenous PGE2 enhances both leptin release and leptin mRNA accumulation by explants of human adipose tissue in primary culture.