Abstract
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Objectives Brown adipose tissue (BAT) is an attractive therapeutic target for diabetes and obesity due to its ability to increase glucose expenditure. However, our knowledge of pathophysiology of BAT and obesity is still at a preliminary stage and needs to be expanded. Using a genetic rat model (ZDF fa/fa) of type-2 diabetes associated with obesity, we aimed to investigate glucose utilization of BAT under insulin stimulation with 18F-FDG PET imaging.
Methods Male Zucker diabetic fatty (ZDF) (n=6) and Male Zucker lean (ZL) control rats (n=6) were studied at age 13 weeks. 18F-FDG PET imaging study was performed at room temperature (23 degrees) under hyperinsulinemic-euglycemic clamp with 12mU/kg/min insulin (Insuman rapid) and variable infusion rates of glucose to maintain euglycemia. Dynamic 35 min PET acquisitions using dedicated small animal PET system (Siemens Inveon) were performed after injection of 37MBq of 18F-FDG via the tail vein. Glucose utilization under insulin stimulation in BAT was calculated from reconstructed PET image data as % of injection dose of FDG activity per tissue weight at 30min after tracer injection. Animals were euthanized immediately after completion of the imaging session, and post mortem organ analysis of BAT was conducted.
Results In hyperinsulinemic-euglycemic state, 18F-FDG PET identified intense interscapular BAT glucose uptake in all ZL control rats. Time activity curves of BAT showed rapid increase of tracer uptake during the initial 10 min after tracer injection followed by stable tracer retention until the end of the imaging session. In contrast, no focally increased FDG uptake was detected in the 35min dynamic scan in ZDF rats. 18F-FDG uptake (%ID/g tissue) of BAT at 30 min after tracer injection was calculated as 0.11±0.05 and 1.08±0.42 (p<0.005) in ZDF diabetic rats and ZL controls, respectively. At the time of dissection, interscapular BAT was easily detected by direct visual inspection in the ZL control rats due to reddish brown color, while BAT in ZDF rats was found as whitish brown. The weight of the BAT was significantly higher in the ZDF rat compared with ZL controls (0.56±0.13g and 0.28±0.07g, p<0.001).
Conclusions Insulin stimulated 18F-FDG uptake was significantly decreased in a rat model of type 2 diabetes and obesity. Our results provide new insight into the relation between diabetes and energy expenditure of BAT.