Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus

Constantin Lapa, Paula Arias-Loza, Nobuyuki Hayakawa, Hiroshi Wakabayashi, Rudolf A. Werner, Xinyu Chen, Tetsuya Shinaji, Ken Herrmann, Theo Pelzer, Takahiro Higuchi

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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.

Original languageEnglish
Article number16795
JournalScientific reports
Issue number1
Publication statusPublished - Dec 1 2017
Externally publishedYes


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Cite this

Lapa, C., Arias-Loza, P., Hayakawa, N., Wakabayashi, H., Werner, R. A., Chen, X., Shinaji, T., Herrmann, K., Pelzer, T., & Higuchi, T. (2017). Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus. Scientific reports, 7(1), [16795]. https://doi.org/10.1038/s41598-017-17148-w