Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5127, USA.
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5127, USA.
Cell Rep. 2018 Jul 24;24(4):809-814. doi: 10.1016/j.celrep.2018.06.082.
Previous studies using genetic mouse models have implicated COX-2 in the browning of white adipose tissues (WATs) in mice during cold exposure. However, COX-2 is important during development, and conventional knockouts (KOs) exhibit many defects, conditioned by genetic background. Similarly, the physiological relevance of transgenic overexpression of COX-2 is questionable. In the present study, we utilized mice in which COX-2 was deleted postnatally, bypassing the consequences of enzyme deficiency during development. Despite activation of thermogenesis and browning of inguinal WAT, cold exposure failed to increase COX-2 expression in the adipose tissues of mice with different genetic backgrounds, and the body temperature response to cold was unaltered in postnatal global COX-2 KOs. Selective disruption of COX-2 in adipose tissues also failed detectably to impact systemic prostaglandin biosynthesis. Browning of inguinal WATs induced by exposure to cold is independent of adipose tissue COX-2.
先前的研究使用遗传小鼠模型表明,环氧化酶-2(COX-2)在冷暴露期间参与了白色脂肪组织(WAT)的棕色化。然而,COX-2 在发育过程中很重要,传统的敲除(KO)会由于遗传背景而表现出许多缺陷。同样,COX-2 的转基因过表达的生理相关性也值得怀疑。在本研究中,我们利用了在出生后敲除 COX-2 的小鼠,从而避免了在发育过程中酶缺乏的后果。尽管产热和腹股沟 WAT 的棕色化被激活,但在具有不同遗传背景的小鼠中,冷暴露并未增加脂肪组织中 COX-2 的表达,而且产后全身性 COX-2 KO 对冷的体温反应也没有改变。脂肪组织中 COX-2 的选择性破坏也未能明显影响全身前列腺素的生物合成。冷暴露诱导的腹股沟 WAT 的棕色化与脂肪组织 COX-2 无关。