Abstract
In mice heterozygous for the cyclooxygenase-2 gene (COX-2+/-) the body weight was enhanced by 33% as compared to homozygous COX-2-/- mice. The weights of the gonadal fat pads in COX-2+/- mice were enhanced by 3.5 to 4.7 fold as compared to COX-2-/- mice and by 1.5 to 3.5 fold as compared to wild-type controls+/+ Serum leptin levels and leptin release by cultured adipose tissue of COX-2+/- mice were both elevated as compared to either control or COX-2-/- animals. The basal release of PGE2 or 6 keto PGF1alpha per fat pad over a 24 h incubation of adipose tissue was reduced by 80% and 95% respectively in tissue from COX-2-/- mice. NS-398, a specific COX-2 inhibitor, inhibited leptin release by 27% in adipose tissue from control mice, 31% in tissue from COX-1-/- mice and by 23% in tissue from COX-2+/- mice while having no effect on leptin release by adipose tissue from COX-2-/- mice. These data indicate that heterozygous COX-2 mice develop obesity which is not secondary to a defect in leptin release by adipose tissue.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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6-Ketoprostaglandin F1 alpha / metabolism
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Adipose Tissue / drug effects
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Adipose Tissue / metabolism*
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Animals
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Body Weight
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Dinoprostone / metabolism
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Epididymis / anatomy & histology
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Female
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Heterozygote
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Humans
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Isoenzymes / genetics*
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Isoenzymes / metabolism
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Leptin / blood
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Leptin / metabolism
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Male
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Membrane Proteins
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Mice
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Mice, Knockout
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Nitrobenzenes / pharmacology
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Obesity / etiology
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Obesity / genetics*
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Obesity / physiopathology
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Organ Size
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Prostaglandin-Endoperoxide Synthases / genetics*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Statistics as Topic
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Sulfonamides / pharmacology
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Leptin
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Membrane Proteins
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Nitrobenzenes
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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6-Ketoprostaglandin F1 alpha
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, mouse
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Dinoprostone