Abstract
Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by 18F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic 18F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. 18F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased 18F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.
Highlights
Since its rediscovery in adult humans in the late 2000s, brown adipose tissue (BAT) has attracted a lot of attention as a potential target to combat obesity, and stimuli for its activation have been investigated in both animal models and humans[4,5,6,7,8,9,10,11,12,13,14]
In hyperinsulinemic-euglycemic state, 18F-FDG PET identified intense inter-scapular tracer uptake consistent with Brown adipose tissue (BAT) glucose utilization in all Zucker lean (ZL) control rats
The 18F-FDG uptake (%ID) of interscapular BAT at 30 min after tracer injection was calculated as 0.045 ± 0.006*,***, 0.28 ± 0.05** and 0.18 ± 0.07 in Zucker diabetic fatty (ZDF)-ND rats, ZL control rats, and ZDF-CR rats, respectively, demonstrating significant differences between each group (*p < 0.01 and **p < 0.001 vs ZDF-CR, and ***p < 0.0001 vs ZDF rats were randomized into a no-restriction (ZDF-ND), Fig. 2B)
Summary
Since its rediscovery in adult humans in the late 2000s, brown adipose tissue (BAT) has attracted a lot of attention as a potential target to combat obesity, and stimuli for its activation have been investigated in both animal models and humans[4,5,6,7,8,9,10,11,12,13,14]. We aimed to investigate BAT glucose utilization in a well-established genetic rat model of type 2 diabetes[20] using 18F-FDG PET imaging under hyperinsulinemic-euglycemic clamping conditions. Rats were set under hyperinsulinemic-euglycemic conditions to stimulated BAT glucose consumption by high serum insulin concentrations during the imaging period[21,22,23], the euglycemic status permitted to avoid interference of different plasma glucose concentrations between diabetic and control animals[24]
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