Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Aim: Brown adipose tissue (BAT) is essential in regulation of energy balance, body temperature and body weight in rodents as in humans. A main BAT activation path leads via β3 adrenoceptors to an increased thyroid hormone (TH) conversion from T4 in T3 followed by mitochondrial heat production. As a direct BAT regulation via TH was not shown before our aim was to prove a direct influence of peripheral TH on BAT by combined [¹⁸F]FDG‐PET/MR measurements and gene expression studies.

Materials and methods: We induced hyperthyroidism in C57BL/6 mice by oral application of L‐thyroxine as well as hypothyroidism by an iodine deficient diet containing propylthiouracil. In these mice as well as in an euthyroid control cohort (each n=3) [18F]FDG‐PET/MR (nanoScan®, Mediso) was performed after i.p. injection of 15 MBq [¹⁸F]FDG. Glucose uptake (SUVmean) in interscapular BAT (iBAT) was measured by using MR‐based VOI analysis (PMOD v. 3.3). In order to evaluate the effects of TH on gene expression patterns in adipose tissue, microarray analyses were performed on visceral, subcutaneous and BAT. Results: Hyperthyroid mice showed a non‐significant increased [¹⁸F]FDG uptake in iBAT compared to the control group (SUVmean 8.78 ± 2.08 and 6.16 ± 0.57, p=0.16 ). In contrast, hypothyroid mice were found with significant reduced FDG uptake in iBAT (SUVmean 3.53 ± 0.65; p<0.01 vs. hyperthyroid and vs. control, respectively). In addition, differential gene expression analysis between the three mice cohorts are pointing to a discrepancy in the expression of brown and beige adipocyte differentiation markers in visceral and subcutaneous adipose tissue in hyper‐ and hypothyroid mice.
Conclusion: These findings confirm the impact of TH on iBAT activity in mice and substantiate the use of [¹⁸F]FDG PET/MR as a valuable tool to map the effects of TH on BAT activity. In addition, this is the first study confirming decreased iBAT activity in hypothyroid mice.
Furthermore, a current clinical study is investigating the translation of these results into humans with thyroid disorders in order to further explore the complex regulation of BAT as a potential treatment target, particularly in obesity. Acknowledgement: The first two authors contributed equally.