Transcriptomic evidence that cortisol alters perinatal epicardial adipose tissue maturation.
Transcriptomic evidence that cortisol alters perinatal epicardial adipose tissue maturation.
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转录组学证据表明皮质醇会改变围产期心外膜脂肪组织的成熟。
DOI：
10.1152/ajpendo.00007.2019
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Keller-Wood,Maureen
中科院分区：
文献类型：
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作者：
Richards,ElaineM;McElhaney,Emily;Zeringue,Katelyn;Joseph,Serene;Keller-Wood,Maureen
母羊妊娠晚期注射皮质醇，模拟母体压力，导致转录组变化，表明后代心脏的成熟和代谢变化发生改变。这项研究调查了皮质醇对心外膜脂肪组织（EAT）的影响，这是一种与成人不良心血管疾病相关的内脏脂肪垫。从妊娠 115 天到足月，用 1 mg·kg−1·day−1 皮质醇治疗怀孕母羊，并从足月胎儿收集 EAT（对照：n= 8，母体皮质醇 1 mg·kg−1·day−1:n= 6）。为了比较皮质醇对 EAT 正常成熟的影响，我们还使用对照胎儿和两周大羔羊（对照：n = 7）的 EAT 模拟了从子宫内到产后生活过渡时 EAT 基因表达的正常变化。转录组模型用于识别因母体皮质醇过度暴露而改变的途径。转录组模型证实了对照胎儿/羔羊足月时 EAT 的棕色脂肪表型以及 2 周时 EAT 向白色脂肪的转变，并强调了免疫反应（包括补体凝血和血清素）在这一转变中的作用。母体皮质醇（1 mg·kg−1·day−1）增加了足月胎儿EAT中的脂质过氧化产物4-羟基壬烯醛，但不影响活化巨噬细胞的数量或库中脂滴的大小；转录组学表明 EAT 的代谢成熟在一定程度上是通过增强免疫反应实现的。
Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 mg·kg−1·day−1cortisol from 115 days gestation to term and EAT collected from term fetuses (control:n= 8, maternal cortisol 1 mg·kg−1·day−1:n= 6). To compare the effects of cortisol to the normal maturation in EAT, we also modeled the normal changes in gene expression in EAT at the transition from in utero to postnatal life using the EAT from control fetuses and from two-week-old lambs (control:n= 7). Transcriptomic modeling was used to identify pathways altered by maternal cortisol overexposure. Transcriptomic modeling confirmed the brown fat phenotype of EAT at term and a transition toward white fat at 2 wk of age in EAT of control fetuses/lambs and highlighted a role of immune responses, including complement coagulation, and serotonin in this transition. Maternal cortisol (1 mg·kg−1·day−1) increased the lipid peroxidation product 4-hydroxynonenal in EAT of term fetuses but did not affect the number of activated macrophages or size of the lipid droplets in the depot; transcriptomics suggested an earlier metabolic maturation of EAT via, in part, increased immune responses.