Lipopolysaccharide-induced leptin release is not mediated by nitric oxide, but is blocked by dexamethasone.
The adipocyte hormone, leptin, has homology with tumor necrosis factor-alpha (TNF-alpha) and the leptin receptor (OB-Rb) has homology with the interleukin(IL)-6 receptor. Lipopolysaccharide (LPS) from gram-negative bacteria stimulates 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 stimulate 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 determine if this release was mediated by nitric oxide (NO), nitroarginine methyl ester (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 on LPS-induced leptin release. On the other hand, dexamethasone (DEX) (0.85 mg/kg), a synthetic glucocorticoid, injected 15 min before LPS, decreased LPS-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, largely block LPS-induced leptin release. Increased release of leptin during infection may contribute to the decreased feeding, altered hormonal release and metabolic changes that occur during infection.
Mastronardi
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CA
Pennington Biomedical Research Center (LSU), Baton Rouge, LA 70808-4124, USA.
Yu
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WH
Rettori
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McCann
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D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D020738:Leptin / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D020738:Leptin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester