Detecting white adipose tissue browning in mice with in vivo R2* mapping at 9.4T MRI.

Abstract

White adipose tissue (WAT) browning is considered a promising strategy to combat obesity and related metabolic diseases. Currently, fat-water fraction (FWF) has been used as a marker for the loss of lipids associated with WAT browning. However, FWF may not be sensitive to metabolic changes and cannot specifically reflect iron-regulated metabolism during browning. Here, we report a non-invasive preclinical imaging approach based on iron content detected by R₂* mapping to assess in-vivo WAT browning in mice. In this study, we investigated the browning of inguinal white adipose tissue (iWAT) induced by long-term CL-316,243 (CL) drug stimulation in mice. We quantified the changes in R₂*, FWF, uncoupling protein 1 (UCP1) expression, and iron content. The iWAT of all mice was dissected for hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for the optical density (OD) of UCP1 and iron content. In in-vivo experiments, a significant increase in R₂* and a decrease in FWF were observed in iWAT after 7 days of CL administration compared to the saline-treated and the baseline groups. Accordingly, in ex-vivo experiments, UCP1 expression and the total iron content in iWAT significantly increased after 7 days of CL stimulation. By pooling all mice data, the UCP1 expression level of iWAT and iron content were found to be highly correlated with R₂* and inversely correlated with FWF. Taken together, R₂* mapping with magnetic resonance imaging (MRI) can serve as a potential imaging tool for assessing iWAT browning, which provides a new diagnostic and therapeutic evaluation tool for metabolic diseases.