Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen's Medical Centre, University Hospital, The University of Nottingham, Nottingham, United Kingdom.
University Hospitals Leicester NHS Trust, Leicester, United Kingdom.
JCI Insight. 2016 Aug 18;1(13):e87460. doi: 10.1172/jci.insight.87460.
Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life.
啮齿动物和新生人类的研究表明,棕色脂肪组织(BAT)在体温控制和能量平衡中发挥重要作用,并在调节体重方面起着关键作用。在这里,我们从新生儿、婴儿和儿童中获取心外膜脂肪组织(EAT)样本,通过应用系统生物学方法来评估其转录组图谱的变化。令人惊讶的是,这些分析表明,向婴儿期的过渡是 EAT 形态发生变化的关键阶段,这反映在大量产热基因转录本(约 10%)的独特表达模式上。我们的研究结果还表明,即使在儿童后期产热基因丰度反弹后,基因表达模式仍代表一个独特的发育阶段。使用加权基因共表达网络分析,我们发现了与 EAT 中基因表达变化和产热能力下降相关的精确的人体测量特异性相关性。此外,这些结果表明,影响细胞途径的转录事件具有顺序,这可能解释了 BAT 数量或活性在成年期的变化。总之,这些结果提供了一个资源,以阐明在生命早期 BAT 进行性发育的基因调控机制。