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 invivo 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 invivo experiments, a significant increase in R2∗ and a decrease in FWF were observed in iWAT after 7days of CL administration compared with the saline-treated and the baseline groups. Accordingly, in exvivo experiments, UCP1 expression and the total iron content in iWAT significantly increased after 7days 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.
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