A UCP1 Near-Infrared Reporter System for Monitoring Adipose “Browning” In Vivo Using Photoacoustic Imaging

Obesity has reached pandemic proportions in the developed world. The discovery that white adipocytes have the capacity to undergo browning to become metabolically-active beige cells has generated significant interest in the field of metabolic medicine. However, the study of adipose tissue browning has been hampered by a lack of imaging modalities that permit longitudinal and non-invasive monitoring of this process. To this end, we designed near infra-red (NIR) fluorescence protein iRFP720-Ucp1 reporter construct, in which the expression of iRFP720 is driven by a mini UCP1 promoter. Non-invasive assessment of adipose beiging during adrenergic stimulation was performed by viral transduction of mouse white adipocytes, followed by multi-spectral optoacoustic imaging technology with ultrasound tomography (MSOT-US). We observed increased iRFP720 fluorescence coupled with attenuated lipid signals upon stimulation. As proof of concept, we validated our approach against the hybrid positron emission tomography combined with magnetic resonance (PET/MR) imaging modality, and quantified the extent of adipose browning by MRI-guided segmentation of PET signals. Notably, the browning extent detected by the iRFP720 reporter system with MSOT-US and the 18-FDG uptake in PET/MR are well correlated with Ucp1 induction. Together, these systems provide platforms for preclinical screening of compounds aimed to promote adipose browning and facilitate the translation of these discoveries into pharmacological treatments for obesity.