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Techniques and Methods

Glucose metabolism in brown adipose tissue determined by deuterium metabolic imaging in rats

International Journal of Obesity volume 44, pages 1417–1427 (2020)Cite this article

Subjects

Abstract

Background/Objectives

Brown adipose tissue (BAT) has gained growing interest as a potential target for treatment of obesity. Currently, the most widely used technique/method for in vivo measurements of BAT activity in humans is 18FDG PET/CT. To supplement these investigations novel radiation-free methods are warranted. Deuterium metabolic imaging (DMI) is a novel modality that combines magnetic resonance spectroscopic (MRS) imaging with deuterium-labelled glucose (2H-glucose). This allows for spatio-temporal and metabolic imaging beyond glucose uptake. We aimed to evaluate if DMI could discriminate glucose metabolism in BAT of cold-acclimatised and thermoneutral rats.

Subjects/Methods

Male Sprague-Dawley rats were housed in a cold environment (9 °C, n = 10) or at thermoneutrality (30 °C, n = 11) for 1 week. For imaging rats were anaesthetized, received a 2H-glucose (1 M, 1.95 g/kg) bolus and DMI was acquired at baseline followed by 20 min time intervals up to 2 h. Furthermore, Dixon MRI was performed for anatomical determination of the interscapular BAT (iBAT) depot along with dynamic contrast enhanced (DCE) MRI to evaluate perfusion.

Results

2H-glucose signal was higher in cold-acclimatised rats compared with thermoneutral rats (p ≤ 0.001) indicating an overall increase in glucose uptake and metabolism. This was in line with a lower fat/water threshold, higher perfusion and increased UCP1 mRNA expression in iBAT (ninefold increment) of cold-acclimatised rats compared with thermoneutral rats.

Conclusions

We find that DMI can discriminate cold-acclimatised and thermoneutral BAT in rats. This is the first study to evaluate BAT activity by DMI, which may open up for the use of the non-radioactive DMI method for BAT measurements in humans.

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Fig. 1: Dixon fat/water MR images with overlay of 2H-labelled metabolites in iBAT.
Fig. 2: Accumulated 2H-labelled signals normalized to the pre-2H-glucose signal in iBAT of cold-acclimatised (n = 10, black circles) and thermoneutral rats (n = 11, white circles).
Fig. 3: 2H-labelled metabolite ratios in iBAT.
Fig. 4: Perfusion in iBAT by dynamic contrast enhanched MRI.
Fig. 5: UCP1 mRNA expression in iBAT biopsy material from thermoneutral (n = 11) and cold-acclimatised (n = 9) rats.

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Acknowledgements

We would like to thank Pia Hornbek and Lenette Pedersen at the Department of Endocrinology and Internal Medicine, Medical Research Lab, Aarhus University Hospital, Denmark, for excellent laboratory assistance.

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200, Aarhus N, Denmark

    Mette Ji Riis-Vestergaard, Steen Bønløkke Pedersen & Bjørn Richelsen

  2. Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Mette Ji Riis-Vestergaard, Steen Bønløkke Pedersen & Bjørn Richelsen

  3. MR Research Center, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Christoffer Laustsen & Christian Østergaard Mariager

  4. GE Healthcare, Munich, Germany

    Rolf F. Schulte

  5. Steno Diabetes Center Aarhus, Aarhus, Denmark

    Steen Bønløkke Pedersen & Bjørn Richelsen

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Contributions

MJRV, CL, SBP and BR conceived and designed the study. MJRV, CL and CØM performed the experiments and acquired the data. MJRV analysed and interpreted the data with input from CL, SBP and BR. MJRV drafted and revised the manuscript with major input from CL, SBP, BR and RFS. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work. MJRV has had full access to the data in the study and final responsibility for the decision to submit for publication.

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Correspondence to Mette Ji Riis-Vestergaard.

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RFS is employed by GE Healthcare, Munich, Germany. The rest of the authors declare no conflicts of interest.

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Riis-Vestergaard, M.J., Laustsen, C., Mariager, C.Ø. et al. Glucose metabolism in brown adipose tissue determined by deuterium metabolic imaging in rats. Int J Obes 44, 1417–1427 (2020). https://doi.org/10.1038/s41366-020-0533-7

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