Brown adipose tissue development and fetal growth

摘要 棕色脂肪组织(BAT)是在出生前发育起来的，在出生时发挥生热功能 分娩后立即达到最高水平。由于非颤动生热的耗能特性， BAT激活在能量代谢和肥胖发展中的作用已经引起了我们的关注 请注意。我们最近的研究表明，蝙蝠/产热作用在晚期显著减少。 怀孕，这对产妇的代谢适应有积极的贡献。在这项研究中，我们观察到一个显著的 UCP1基因敲除坝的胎儿体重减轻。由于BAT在新生儿中的独特作用 生活中，这一耐人寻味的表型让我们进行了一系列实验，以确定胎儿蝙蝠对 胎儿发育。通过敲除Ucp1基因和基因消融胎儿中的棕色脂肪细胞，我们的 初步研究产生了一丝确凿的证据表明胎儿蝙蝠的发育和激活 与胎儿生长密切相关。初步研究还表明，胎儿Ucp1基因敲除和BAT消融 在不改变胎盘结构的情况下显著减轻胎盘重量。猪的代谢表型 Ucp1/-和BAT缺失型胎儿血糖浓度升高和血胰岛素水平下降 表明这些胎儿的胰岛发育存在缺陷。总之，这些初步数据让我们得出了 假设胎儿蝙蝠、胎盘和胎儿胰岛之间存在器官内串扰 怀孕晚期。通过这些串扰，宫内新陈代谢、胎儿组织发育和生长 受监管的。将进行一系列动物研究来验证这一假设。我们将使用遗传老鼠 妊娠晚期蝙蝠/胎盘/胰岛串扰的模型和体外实验方法。国家-- 将使用最先进的系统来确定胎儿棕色脂肪细胞是否分泌独特的蝙蝠激素，并通过 与其他胎儿器官相互作用。这一建议的成功将为今后的研究奠定基础 阐明胎儿蝙蝠在宫内代谢和胎儿生长发育中的作用。

SUMMARY Brown adipose tissue (BAT) is developed before birth and exerts the thermogenic function at the maximal level immediately after delivery. Due to the energy-consuming nature of non-shivering thermogenesis, the contribution of BAT activation in energy metabolism and the development of obesity has caught our attention. Our recent study demonstrated that BAT/thermogenesis is significantly reduced during late pregnancy, which actively contributes to maternal metabolic adaptation. In this study, we observed a significant reduction of fetal body weight from UCP1 gene knockout dams. Due to the unique function of BAT in neonatal life, this intriguing phenotype led us to carry out a series of experiments to determine the effect of fetal BAT on fetal development. By knocking out the Ucp1 gene and genetic ablating brown adipocytes in fetuses, our preliminary study generates a shred of solid evidence indicating that fetal BAT development and activation are closely associated with fetal growth. The initial studies also showed that fetal Ucp1 knockout and BAT ablation significantly reduced placenta weight without alternation in placental structure. The metabolic phenotypes of elevated blood glucose concentrations and decreased blood insulin levels in Ucp1-/- and BAT-null fetuses suggest a defect in fetal islet development in these fetuses. Together, these preliminary data led us to hypothesize that there is intra-organ crosstalk between fetal BAT, the placenta, and fetal pancreatic islets at late pregnancy. Through these crosstalks, intrauterine metabolism, fetal tissue development, and growth are regulated. A series of animal studies will be performed to verify this hypothesis. We will use genetic mouse models and in vitro approaches to demonstrate the BAT/Placenta/Islet crosstalk in late pregnancy. The state- of-art system will be employed to determine if fetal brown adipocytes secret unique batokines and through which interact with other fetal organs. This proposal's success will lay down a foundation for future studies to elucidating the function of fetal BAT in intrauterine metabolism and fetal growth.