Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging.
Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging.
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DOI：
10.1162/153535003765276273
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Frangioni, John V
中科院分区：
文献类型：
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作者：
Nakayama, Akira;Bianco, Antonio C;Frangioni, John V
棕色脂肪组织（BAT;棕色脂肪）是人类新生儿和其他小型哺乳动物适应性产热的主要部位。对于产热来说，最重要的是血管灌注，它控制着BAT中冷血液的流入和热血液的流出。我们已经开发了一种光学方法的定量成像BAT灌注在活的，完整的动物使用七甲川吲哚菁IR-786和近红外（NIR）荧光灯。我们提出了一个详细的分析IR-786的物理，化学和细胞特性，其生物分布和药代动力学，以及其吸收到BAT。使用纯合缺失II型碘代甲状腺原氨酸脱碘酶或纯合缺失解偶联蛋白（UCPs）1和2的转基因动物，我们证明BAT灌注可以无创，准确和可重复地测量。使用这些技术，我们表明，UCP-1/-2敲除动物，当与野生型动物相比，有一个较高的基线灌注BAT，但类似的最大反应β 3受体激动剂。这些结果表明，补偿UCP缺失介导的，在一定程度上，由BAT灌注的控制。总而言之，现在可以使用近红外荧光无创地测量BAT灌注，并且可以在活体动物中以相对高的通量筛选产热的药理学调节剂。
Brown adipose tissue (BAT; brown fat) is the principal site of adaptive thermogenesis in the human newborn and other small mammals. Of paramount importance for thermogenesis is vascular perfusion, which controls the flow of cool blood in, and warmed blood out, of BAT. We have developed an optical method for the quantitative imaging of BAT perfusion in the living, intact animal using the heptamethine indocyanine IR-786 and near-infrared (NIR) fluorescent light. We present a detailed analysis of the physical, chemical, and cellular properties of IR-786, its biodistribution and pharmacokinetics, and its uptake into BAT. Using transgenic animals with homozygous deletion of Type II iodiothyronine deiodinase, or homozygous deletion of uncoupling proteins (UCPs) 1 and 2, we demonstrate that BAT perfusion can be measured noninvasively, accurately, and reproducibly. Using these techniques, we show that UCP -1/-2 knockout animals, when compared to wild-type animals, have a higher baseline perfusion of BAT but a similar maximal response to beta 3-receptor agonist. These results suggest that compensation for UCP deletion is mediated, in part, by the control of BAT perfusion. Taken together, BAT perfusion can now be measured noninvasively using NIR fluorescent light, and pharmacological modulators of thermogenesis can be screened at relatively high throughput in living animals.