In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.
In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.
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DOI：
10.1161/circimaging.112.975607
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发表时间：
2012-09-01
期刊：
影响因子：
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通讯作者：
Scherrer-Crosbie M
中科院分区：
文献类型：
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作者：
Baron DM;Clerte M;Brouckaert P;Raher MJ;Flynn AW;Zhang H;Carter EA;Picard MH;Bloch KD;Buys ES;Scherrer-Crosbie M
正在广泛研究增加棕色脂肪组织（BAT）体积和激活的干预措施，作为降低肥胖受试者体重的疗法。在动物模型和人类中监测这些疗法的非侵入性方法很少见。我们研究了在小鼠中进行的对比超声（CU）是否可以检测BAT并通过监测BAT血流来测量其激活。验证后，CU被用来研究解偶联蛋白1（UCP 1）和一氧化氮合酶在BAT血流急性调节中的作用。通过测量连续输注的造影剂微泡的信号强度来评估具有CU的小鼠（n=64）中肩胛间BAT的血流。通过CU估计的BAT血流量在基线时为0.5±0.1（平均值±SEM）dB/s，在去甲肾上腺素（NE，1 μg·kg−1·min−1）刺激BAT期间增加15倍。使用CU评估BAT血流与使用荧光微球进行的评估相关（R2=0.86，p<0.001）。为了评估是否需要完整的BAT激活来增加BAT血流量，在BAT激活受损的UCP 1缺陷（UCP 1 −/−）小鼠中进行CU。与野生型小鼠相比，去甲肾上腺素输注在UCP 1 −/−小鼠中诱导的BAT血流量增加较小。最后，我们研究了NOS是否在急性NE诱导的BAT血流变化中发挥作用。NOS 3的遗传和药理学抑制减弱了NE诱导的BAT血流量增加。这些结果表明，CU可以检测小鼠中的BAT，并估计BAT功能差异的小鼠中的BAT血流量。
Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 (UCP1) and nitric oxide synthases in the acute regulation of BAT blood flow. Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (NE, 1 μg·kg−1·min−1). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R2=0.86, p<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in UCP1-deficient (UCP1−/−) mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in UCP1−/− mice than in wild-type mice. Finally, we investigated whether NOS played a role in acute NE-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of NOS3 attenuated the NE-induced increase in BAT blood flow. These results indicate that CU can detect BAT in mice, and estimate BAT blood flow in mice with functional differences in BAT.