Lipopolysaccharide-induced leptin release is not mediated by nitric oxide,but is blocked by dexametbasone

The adipocyte hormone, leptin, has homology with tumor necrosis factor-alph a (TNF-alpha) and the leptin receptor (OB-Rb) has homology with the interle ukin(IL)-6 receptor, Lipopolysaccharide (LPS) from gram-negative bacteria s timulates the release of many pro-inflammatory cytokines, such as TNF-alpha , IL-1 and IL-6, among others. To test the hypothesis that LPS would also s timulate the release of leptin, LPS (0.6 mg/kg) was injected intravenously into conscious male rats bearing external jugular venous catheters. Vehicle (0.9% NaCl) was injected into control animals. Blood samples (0.3 ml) were drawn immediately before injection and every 10 min afterwards for 120 min . Plasma leptin concentrations increased gradually in the LPS-treated rats, reaching a peak at 120 min of nearly twice the starting level. To determin e if this release was mediated by nitric oxide (NO), nitroarginine methyl e ster (NAME), an inhibitor of NO synthase, was injected at doses of 11 or 23 mg/kg (i.v.). The lower dose decreased plasma leptin slightly, whereas the higher dose of NAME increased plasma leptin at 110 min but had no effect o n LPS-induced leptin release. On the other hand, dexamethasone (DEX) (0.85 mg/kg), a synthetic glucocorticoid, injected 15 min before LPS, decreased L PS-induced leptin release by 80% (p < 0.001). The results indicate that LPS is a stimulant of leptin release, that NO has little control over basal or LPS-induced leptin release, but that glucocorticoids, epitomized by DEX, l argely block LPS-induced leptin release. increased release of leptin during infection may contribute to the decreased feeding, altered hormonal releas e and metabolic changes that occur during infection. Copyright (C) 2000 S. Karger AG, Basel.