Odegaard Justin I, Lee Min-Woo, Sogawa Yoshitaka, Bertholet Ambre M, Locksley Richard M, Weinberg David E, Kirichok Yuriy, Deo Rahul C, Chawla Ajay
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
Department of Physiology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
Cell. 2016 Aug 11;166(4):841-854. doi: 10.1016/j.cell.2016.06.040. Epub 2016 Jul 21.
For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the "alarmin" IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period. PAPERCLIP.
对于胎盘哺乳动物而言，从子宫内的母体环境过渡到出生后的生活需要激活产热作用以维持其核心体温。这主要是通过在棕色和米色脂肪细胞中诱导解偶联蛋白1（UCP1）来实现的，棕色和米色脂肪细胞是解偶联呼吸的主要场所。尽管其很重要，但胎盘哺乳动物如何使它们的产热脂肪细胞参与出生后的解偶联呼吸尚不清楚。在这里，我们提供证据表明，“警报素”白细胞介素-33（IL-33），一种激活2型免疫反应的核细胞因子，使棕色和米色脂肪细胞进行解偶联呼吸。我们发现，在没有IL-33或ST2的情况下，米色和棕色脂肪细胞正常发育，但无法表达剪接形式合适的Ucp1 mRNA，导致UCP1蛋白缺失以及解偶联呼吸和体温调节受损。总之，这些数据表明IL-33和ST2作为一种发育开关，在围产期许可产热作用。回形针。
