Obesity is induced in mice heterozygous for cyclooxygenase-2

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 PGE, or 6 keto PGF(1 alpha) 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. (C) 2001 Elsevier Science Inc. All rights reserved.