Fain J N, Ballou L R, Bahouth S W
Department of Molecular Sciences, College of Medicine, The University of Tennessee Health Science Center, Memphis 38163, USA.
Prostaglandins Other Lipid Mediat. 2001 Jul;65(4):199-209. doi: 10.1016/s0090-6980(01)00136-8.
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.
在环氧化酶-2基因杂合的小鼠（COX-2+/-）中，与纯合的COX-2-/-小鼠相比，体重增加了33%。与COX-2-/-小鼠相比，COX-2+/-小鼠性腺脂肪垫的重量增加了3.5至4.7倍，与野生型对照+/+相比增加了1.5至3.5倍。与对照或COX-2-/-动物相比，COX-2+/-小鼠培养的脂肪组织的血清瘦素水平和瘦素释放均升高。在COX-2-/-小鼠的组织中，脂肪组织在24小时孵育期间每个脂肪垫的PGE2或6-酮-PGF1α基础释放分别降低了80%和95%。NS-398是一种特异性COX-2抑制剂，它抑制对照小鼠脂肪组织中瘦素释放的27%，COX-1-/-小鼠组织中瘦素释放的31%，以及COX-2+/-小鼠组织中瘦素释放的23%，而对COX-2-/-小鼠脂肪组织的瘦素释放没有影响。这些数据表明，杂合的COX-2小鼠会发生肥胖，这并非继发于脂肪组织瘦素释放缺陷。
