Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons
Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons
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DOI：
10.1038/ijo.2017.82
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发表时间：
2017-08-01
影响因子：
4.9
通讯作者：
Clarke, G. D.
中科院分区：
文献类型：
--
作者：
Kuo, A. H.;Li, J.;Clarke, G. D.
发育规划研究表明，糖皮质激素可以改变胎儿的发育。我们假设，在胎儿生命的剂量和阶段给怀孕的狒狒服用合成糖皮质激素(SGC)倍他米松的剂量和阶段与人类产科的做法相同，以降低早产儿的发病率和死亡率，并规划脂代谢。在10岁的雄性狒狒(相当于40只人类)中，在胎儿时期暴露于倍他米松或生理盐水中，我们用磁共振成像和光谱分析对心包脂肪和肝脏脂肪含量进行了量化。与大多数接触SGC的人类新生儿一样，SGC的后代也是足月出生的。心包脂肪厚度(7.70±-3.6mmvs3.1+/-1.1mmM+/-Sd；P=0.022；n=5)和肝脂肪酸(13.3+/-11.0%vs2.5+/-2.2%；P=0.046；n=5)在无出生体重和当前身体形态差异的情况下增加。我们的结果表明，产前SGC治疗导致了中年灵长类后代脂肪沉积和成体成分的异常。引起关注的是，这种程度的心包和肝脏脂肪堆积可能导致有害的局部脂肪毒性。总而言之，sGC的发育规划产生了一种中年代谢性肥胖但体重正常的表型。以前的研究表明，对一些编程挑战的性二态反应，因此女性研究是必要的。
Developmental programming studies indicate that glucocorticoids modify fetal development. We hypothesized that administration of the synthetic glucocorticoid (sGC) betamethasone to pregnant baboons at doses and stages of fetal life equivalent to human obstetric practice to decrease premature offspring morbidity and mortality, programs lipid metabolism. In 10-year-old male baboons (human equivalent 40) exposed in fetal life to betamethasone or saline, we quantified pericardial fat and hepatic lipid content with magnetic resonance imaging and spectroscopy. sGC offspring delivered at term as do most sGC-exposed human neonates. Pericardial fat thickness (7.7 +/- 3.6 mm vs 3.1 +/- 1.1 mm, M +/- s.d.; P = 0.022; n = 5) and hepatic fatty acids (13.3 +/- 11.0% vs 2.5 +/- 2.2%; P = 0.046; n = 5) increased following sGC without birth weight or current body morphometric differences. Our results indicate that antenatal sGC therapy caused abnormal fat deposition and adult body composition in mid-life primate offspring. The concern raised is that this degree of pericardial and hepatic lipid accumulation can lead to harmful local lipotoxicity. In summary, developmental programing by sGC produces a mid-life metabolically obese but normal weight phenotype. Prior studies show sexually dimorphic responses to some programming challenges thus female studies are necessary.