Developmental programming: impact of prenatal testosterone excess on insulin sensitivity, adiposity, and free fatty acid profile in postpubertal female sheep.
Developmental programming: impact of prenatal testosterone excess on insulin sensitivity, adiposity, and free fatty acid profile in postpubertal female sheep.
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DOI：
10.1210/en.2012-2145
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发表时间：
2013-03
期刊：
影响因子：
4.8
通讯作者：
A. Veiga-Lopez;Jacob Moeller;D. Patel;Wen Ye;Anthony Pease;J. Kinns;Vasantha Padmanabhan
中科院分区：
文献类型：
--
作者：
A. Veiga-Lopez;Jacob Moeller;D. Patel;Wen Ye;Anthony Pease;J. Kinns;Vasantha Padmanabhan
产前T过量会导致生殖和代谢紊乱，包括胰岛素抵抗，这是多囊卵巢综合征女性的特征。这项研究测试了是否增加内脏脂肪，脂肪细胞大小，总游离脂肪酸的基础上看到产前T治疗的雌性绵羊的胰岛素抵抗。在大约16个月大时，分别通过高胰岛素正葡萄糖钳夹和计算机断层扫描测定对照组和产前T治疗组雌性动物的胰岛素抵抗和脂肪组织分配。三个月后，测定脂肪细胞大小和游离脂肪酸组成。结果显示，在青春期后的时间点测试，胰岛素敏感性增加，内脏脂肪和脂肪细胞的大小在SC和内脏隔室减少，和循环棕榈酸增加产前T-治疗的女性相对于对照组。在平行研究中，20个月大的产前T治疗的女性往往有增加的基础胰岛素与葡萄糖的比例。相对于早期发现产前接受T治疗的女性在生命早期和成年期胰岛素敏感性降低，青春期后胰岛素敏感性增加和肥胖减少的这些发现表明存在一段发育适应期。几个月后观察到的游离脂肪酸代谢中断对应于产前T处理动物的胰岛素敏感性指数似乎向胰岛素抵抗转变的时间点。总之，目前的研究结果，改善胰岛素敏感性和减少内脏肥胖在青春期后产前T-治疗的羊相对于我们的早期研究结果，降低胰岛素敏感性在出生后早期和成年期是一个时期的发展适应的指示。
Prenatal T excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested whether increases in visceral adiposity, adipocyte size, and total free fatty acids underlie the insulin resistance seen in prenatal T-treated female sheep. At approximately 16 months of age, insulin resistance and adipose tissue partitioning were determined via hyperinsulinemic euglycemic clamp and computed tomography, respectively, in control and prenatal T-treated females. Three months later, adipocyte size and free fatty acid composition were determined. Results revealed that at the postpubertal time points tested, insulin sensitivity was increased, visceral adiposity and adipocyte size in both the sc and the visceral compartments were reduced, and circulating palmitic acid was increased in prenatal T-treated females relative to controls. In parallel studies, 20-month-old prenatal T-treated females tended to have increased basal insulin to glucose ratio. Relative to earlier findings of reduced insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in free fatty acid metabolism a few months later correspond to a time point when the insulin sensitivity indices of prenatal T-treated animals appear to shift toward insulin resistance. In summary, current findings of improved insulin sensitivity and reduced visceral adiposity in postpubertal prenatal T-treated sheep relative to our earlier findings of reduced insulin sensitivity during early postnatal life and adulthood are indicative of a period of developmental adaptation.