Women's Health Academic Centre, King's College London, London, SE1 1UL, United Kingdom.
Institute of Reproductive and Developmental Biology, Imperial College London, London, W12 0NN, United Kingdom.
Sci Rep. 2017 Sep 6;7(1):10671. doi: 10.1038/s41598-017-10979-7.
Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT phenotype is lost in murine pregnancy, while there is a gain of white adipose tissue (WAT)-like features. This is characterised by reduced thermogenic capacity and mitochondrial content, accompanied by increased levels of markers of WAT and lipid accumulation. Surgical ablation of BAT prior to conception caused maternal and fetal hyperlipidemia, and consequently larger fetuses. We show that BAT phenotype is altered from day 5 of gestation, implicating early pregnancy factors, which was confirmed by reduced expression of BAT markers in progesterone challenged oophorectomised mice. Moreover, in vitro data using primary BAT cultures show a direct impact of progesterone on expression of Ucp1. These data demonstrate that progesterone mediates a phenotypic change in BAT, which contributes to the gestational metabolic environment, and thus overall fetal size.
妊娠伴随着深刻的母体代谢变化，这对于胎儿的生长和发育是必要的，由作用于代谢器官的生殖信号介导。然而，棕色脂肪组织（BAT）在调节妊娠代谢中的作用尚不清楚。我们发现，在妊娠期间，BAT 表型在小鼠中消失，而出现了类似于白色脂肪组织（WAT）的特征。其特征是产热能力和线粒体含量降低，同时伴随着 WAT 标志物和脂质积累水平的增加。在受孕前进行 BAT 手术消融会导致母体和胎儿的血脂异常，从而导致胎儿更大。我们发现，BAT 表型从妊娠第 5 天开始改变，这暗示了早期妊娠因素，这一结果通过孕激素刺激卵巢切除小鼠中 BAT 标志物表达减少得到了证实。此外，使用原代 BAT 培养物的体外数据表明，孕激素直接影响 Ucp1 的表达。这些数据表明，孕激素介导了 BAT 的表型变化，这有助于妊娠代谢环境，从而影响整体胎儿大小。
