Abstract
There is rising interest in recruitment of brown adipocytes into white adipose tissue (WAT) as a means to augment energy expenditure for weight reduction, but progress in this area requires a method to directly image energy consumption of WAT in living subjects. We thus investigated the ability of 18F-FDG PET/CT to monitor WAT browning in mice. Methods: C57BL/6 mice were treated daily with the β3 adrenergic agonist CL316,243 (1 mg/kg) for 1, 4, 7, or 10 days. Control animals received saline. 18F-FDG micro-PET/CT was serially performed at baseline and during treatment at 1 h after CL316,243 injection. Following sacrifice, interscapular brown adipose tissue (BAT) and WAT depots were extracted, weighed and measured for uptake. Tissues underwent immune staining, and UCP1 content was quantified by Western blotting. Results: PET/CT showed very low 18F-FDG uptake in both BAT and inguinal WAT at baseline. BAT uptake was substantially increased by a single stimulation with CL316,243. Uptake in inguinal WAT was only modestly elevated by the first stimulation, but uptake gradually increased to BAT level by prolonged stimulation. Ex-vivo measurements recapitulated the PET findings, and measured uptakes in other WAT depots were similar to inguinal WAT. WAT browning by prolonged stimulation was confirmed by a substantial increase of UPC1, COX4 and PRDM16 staining as markers brown adipocytes. UCP1 content, which served as a measure for extent of browning, was low in baseline inguinal WAT but linearly increased over 10 days of CL316,243 injection. Finally, image-based and ex vivo measured 18F-FDG uptake in inguinal WAT correlated well with UCP1 content. Conclusions: 18F-FDG PET/CT has the capacity to monitor brown adipocyte recruitment into WAT depots in vivo, and may thus be useful for screening the efficacy of strategies to promote WAT browning, as well as help delineate its impact on energy expenditure by glucose utilization.
- Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.