Kuo A H, Li J, Li C, Huber H F, Schwab M, Nathanielsz P W, Clarke G D
Department of Radiology and Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Int J Obes (Lond). 2017 Aug;41(8):1299-1302. doi: 10.1038/ijo.2017.82. Epub 2017 Mar 24.
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.
发育编程研究表明，糖皮质激素会改变胎儿发育。我们假设，在孕期给狒狒注射合成糖皮质激素（sGC）倍他米松，其剂量和胎儿发育阶段与人类产科实践相当，以降低早产后代的发病率和死亡率，这会对脂质代谢进行编程。在胎儿期暴露于倍他米松或生理盐水的10岁雄性狒狒（相当于人类40岁）中，我们用磁共振成像和光谱法对心包脂肪和肝脏脂质含量进行了量化。sGC后代足月出生，就像大多数暴露于sGC的人类新生儿一样。sGC处理后，心包脂肪厚度（7.7±3.6毫米对3.1±1.1毫米，平均值±标准差；P=0.022；n=5）和肝脏脂肪酸（13.3±11.0%对2.5±2.2%；P=0.046；n=5）增加，而出生体重或当前身体形态测量无差异。我们的结果表明，产前sGC治疗导致中年灵长类后代出现异常脂肪沉积和成年身体组成。令人担忧的是，这种程度的心包和肝脏脂质积累会导致有害的局部脂毒性。总之，sGC的发育编程产生了中年代谢性肥胖但体重正常的表型。先前的研究表明，对某些编程挑战存在性别差异反应，因此有必要进行女性研究。
