Stimulation of leptin release by arachidonic acid and prostaglandin E-2 inadipose tissue from obese humans

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 ov er a 48-hour incubation in primary culture. We found that arachidonic acid or prostaglandin E-2 (PGE(2)) stimulated leptin release by explants of subc utaneous adipose tissue from obese humans. The stimulatory effect of arachi donic acid on leptin formation was blocked by NS-398, a cyclooxygenase-2 (C OX-2) inhibitor. There was appreciable release of PGE(2) to the medium over 48 hours, and this was inhibited by 99% in the presence of 200 nmol/L dexa methasone or 5 mu mol/L NS-398. The increase in PGE(2) release correlated w ith 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 lep tin mRNA at 48 hours was reduced by 28% if PGE(2) was added in the absence of dexamethasone, while in the presence of dexamethasone, the amount of lep tin mRNA was enhanced by 156%. These data suggest that when upregulation of COX-2 is blocked by dexamethasone, exogenous PGE(2) enhances both leptin r elease and leptin mRNA accumulation by explants of human adipose tissue in primary culture. Copyright (C) 2001 by W.B. Saunders Company.