Stimulation of leptin release by arachidonic acid and prostaglandin E(2) in adipose 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 over a 48-hour incubation in primary culture. We found that arachidonic acid or prostaglandin E(2) (PGE(2)) stimulated leptin release by explants of subcutaneous adipose tissue from obese humans. The stimulatory effect of arachidonic acid on leptin formation was blocked by NS-398, a cyclooxygenase-2 (COX-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 dexamethasone or 5 micromol/L NS-398. The increase in PGE(2) release correlated with 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 leptin 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 leptin mRNA was enhanced by 156%. These data suggest that when upregulation of COX-2 is blocked by dexamethasone, exogenous PGE(2) enhances both leptin release and leptin mRNA accumulation by explants of human adipose tissue in primary culture.
Fain
J N
JN
Department of Biochemistry, College of Medicine, University of Tennessee, Memphis, TN 38163, USA.
Leffler
C W
CW
Cowan
G S
GS
Buffington
C
C
Pouncey
L
L
Bahouth
S W
SW
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D020738:Leptin; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; D003907:Dexamethasone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone