Regulation of leptin release and lipolysis by PGE 2 in rat adipose tissue

Abstract

The role of eicosanoids formed by adipose tissue from rats was examined in the presence of the specific cyclooxygenase-2 inhibitor NS-398. This agent totally blocked the release of prostaglandin E 2 (PGE 2) by rat adipose tissue over a 24-h incubation in primary culture. The final concentration of PGE 2 after 24 h was 12 nM, and half-maximal inhibition of PGE 2 formation required 35 nM NS-398. While inhibition of PGE 2 formation by NS-398 had no effect on basal leptin release or lipolysis, it enhanced the lipolytic action of 10 nM isoproterenol by 36%. The in vivo administration of PGE 2 doubled serum leptin. PGE 2 also directly stimulated leptin release by rat adipose tissue incubated in the presence of 25 nM dexamethasone, which inhibited endogenous PGE 2 formation by 94%. The inhibition of lipolysis as well as the stimulation of leptin release by PGE 2 were mimicked by N 6-cyclopentyladenosine (CPA). These data indicate that exogenous PGE 2 can stimulate leptin release by adipose tissue when the basal formation of PGE 2 is blocked by dexamethasone. However, while the endogenous formation of PGE 2 does not appear to regulate basal lipolysis or leptin release, it may play a role in the activation of lipolysis by catecholamines.