Xin Hui Derryn Chan, Ghayathri Balasundaram, Amalina Binte Ebrahim Attia, Julian L Goggi, Boominathan Ramasamy, Weiping Han, Malini Olivo, and Shigeki Sugii Multimodal Imaging Approach to Monitor Browning of Adipose Tissue In Vivo J. Lipid Res. jlr.D083410. First Published on April 13, 2018, doi:10.1194/jlr.D083410
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 lack of imaging tools that allow longitudinal and non-invasive 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 express near infrared fluorescence protein iRFP720 driven under a Ucp1 promoter in mouse by viral transduction, and use multispectral optoacoustic imaging technology with ultrasound tomography (MSOT-US) to assess adipose beiging during adrenergic stimulation. We observe increased iRFP720 fluorescence, coupled with attenuated lipid signals in stimulated animals. As a proof of concept, we validate our approach against the hybrid positron emission tomography combined with magnetic resonance (PET/MR) imaging modality, and quantify the extent of adipose browning by MRI-guided segmentation of 18F-FDG 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.
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