Multimodal imaging approach to monitor browning of adipose tissue in vivo
Multimodal imaging approach to monitor browning of adipose tissue in vivo
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DOI：
10.1194/jlr.d083410
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发表时间：
2018-06-01
影响因子：
6.5
通讯作者：
Sugii, Shigeki
中科院分区：
文献类型：
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作者：
Chan, Xin Hui Derryn;Balasundaram, Ghayathri;Sugii, Shigeki
白色脂肪细胞可以经过褐变过程变成代谢活跃的米色细胞，这一发现引起了人们对对抗肥胖的极大兴趣。然而，由于缺乏对体内脂肪褐变过程进行纵向和无创监测的成像工具，对脂肪褐变的研究一直受到阻碍。在这里，我们报告了一种临床前成像方法来检测肾上腺素能刺激下米色脂肪细胞的发育。在这种方法中，我们通过病毒转导，在解偶联蛋白-1 （Ucp1）启动子的驱动下，在小鼠体内表达近红外荧光蛋白iRFP720，并使用超声断层扫描（MSOT-US）多光谱光声成像技术来评估肾上腺素能刺激期间的脂肪北京。我们观察到在720 nm处光声信号增加，同时脂质信号减弱。作为概念验证，我们针对混合正电子发射断层扫描结合磁共振（PET/MR）成像模式验证了我们的方法，并通过mri引导的2-脱氧-2- f -18-氟葡萄糖摄取信号的分割来量化脂肪褐变的程度。MSOT-US和PET/MR检测的褐变程度与Ucp1诱导密切相关。总之，这些系统为临床前筛选提供了巨大的机会，旨在识别促进脂肪褐变的化合物，并将这些发现转化为人类的临床研究。
The discovery that white adipocytes can undergo a browning process to become metabolically active beige cells has attracted significant interest in the fight against obesity. However, the study of adipose browning has been impeded by a lack of imaging tools that allow longitudinal and noninvasive monitoring of this process in vivo. Here, we report a preclinical imaging approach to detect development of beige adipocytes during adrenergic stimulation. In this approach, we expressed near-infrared fluorescent protein, iRFP720, driven under an uncoupling protein-1 (Ucp1) promoter in mice by viral transduction, and used multispectral optoacoustic imaging technology with ultrasound tomography (MSOT-US) to assess adipose beiging during adrenergic stimulation. We observed increased photoacoustic signal at 720 nm, coupled with attenuated lipid signals in stimulated animals. As a proof of concept, we validated our approach against hybrid positron emission tomography combined with magnetic resonance (PET/MR) imaging modality, and quantified the extent of adipose browning by MRI-guided segmentation of 2-deoxy-2-F-18-fluoro-d-glucose uptake signals. The browning extent detected by MSOT-US and PET/MR are well correlated with Ucp1 induction. Taken together, these systems offer great opportunities for preclinical screening aimed at identifying compounds that promote adipose browning and translation of these discoveries into clinical studies of humans.