Obesity is induced in mice heterozygous for cyclooxygenase-2

Prostaglandins Other Lipid Mediat. 2001 Jul;65(4):199-209. doi: 10.1016/s0090-6980(01)00136-8.

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

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Body Weight
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / metabolism
  • Epididymis / anatomy & histology
  • Female
  • Heterozygote
  • Humans
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Leptin / blood
  • Leptin / metabolism
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Nitrobenzenes / pharmacology
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / physiopathology
  • Organ Size
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Statistics as Topic
  • Sulfonamides / pharmacology

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Leptin
  • Membrane Proteins
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • 6-Ketoprostaglandin F1 alpha
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Dinoprostone