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 noninvasive 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 H&E staining and immunohistochemistry for the absorbance 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 with 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 was found to be highly correlated with R2∗ and inversely correlated with FWF. Taken together, R2∗ may serve as a potential imaging biomarker for assessing WAT browning, which provides a new diagnostic and therapeutic evaluation tool for metabolic diseases.

Keywords

• white adipose tissue
• browning
• R2∗
• iron
• UCP1