# Curcumin analogues as selective fluorescence imaging probes for brown adipose tissue and monitoring browning

## TL;DR

Researchers developed a new imaging probe, CRANAD-29, that can selectively visualize brown fat and track its activation in mice.

## Contribution

A novel curcumin analogue, CRANAD-29, was designed with improved BAT selectivity and emission properties for imaging.

## Key findings

- CRANAD-29 shows significantly improved selectivity for brown adipose tissue over white adipose tissue.
- The probe can monitor BAT activation in diabetic mice and browning of subcutaneous WAT induced by β3-adrenoceptor agonists.
- Stereo-hindrance modifications enhanced the uptake and emission properties of the probe.

## Abstract

Manipulation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can be promising new approaches to counter metabolic disorder diseases in humans. Imaging probes that could consistently monitor BAT mass and browning of WAT are highly desirable. In the course of our imaging probe screening, we found that BAT could be imaged with curcumin analogues in mice. However, the poor BAT selectivity over WAT and short emissions of the lead probes promoted further lead optimization. Limited uptake mechanism studies suggested that CD36/FAT (fatty acid transporter) probably contributed to the facilitated uptake of the probes. By increasing the stereo-hindrance of the lead compound, we designed CRANAD-29 to extend the emission and increase the facilitated uptake, thus increasing its BAT selectivity. Our data demonstrated that CRANAD-29 had significantly improved selectivity for BAT over WAT, and could be used for imaging BAT mass change in a streptozotocin-induced diabetic mouse model, as well as for monitoring BAT activation under cold exposure. In addition, CRANAD-29 could be used for monitoring the browning of subcutaneous WAT (sWAT) induced by β3-adrenoceptor agonist CL-316, 243.