Eicosanoids as endogenous regulators of leptin release and lipolysis by mouse adipose tissue in primary culture

Prostaglandin E-2 (PGE(2)) stimulated leptin release over a 24-h incubation of mouse adipose tissue in primary culture. The maximal stimulation of lep tin release was seen with 100 nm PGE(2). The role of endogenous eicosanoids in the regulation of lipolysis and leptin formation was examined in the pr esence of NS-398, a selective cyclooxygenase-2 inhibitor. NS-398 at a conce ntration of 5 mu M enhanced lipolysis by 30% and lowered leptin release by 24%. This concentration of NS-398 almost completely inhibited PGE(2) format ion. An inhibition of basal lipolysis by PGE(2) or N-6-cyclopentyladenosine (CPA) was seen in the presence but not in the absence of NS-398. CPA, whos e receptor, like that of PGE(2) inhibits cyclic AMP accumulation in adipose tissue, also enhanced leptin release. These data indicate that PGE(2) can stimulate leptin release and suggest that endogenous eicosanoids affect bot h lipolysis and leptin formation by mouse adipose tissue.