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Norepinephrine transporter availability in brown fat is reduced in obesity: a human PET study with [11C] MRB

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Abstract

The energy-dissipating properties of brown adipose tissue (BAT) have been proposed as therapeutic targets for obesity and diabetes. Little is known about basal BAT activity. Capitalizing on the dense sympathetic innervation of BAT, we have previously shown that BAT can be detected in humans under resting room temperature (RT) conditions by using (S,S)-11C–O-methylreboxetine (MRB), a selective ligand for the norepinephrine transporter (NET). In this study, we determine whether MRB labeling of human BAT is altered by obesity. Fifteen healthy, nondiabetic Caucasian women (nine lean, age 25.6 ± 1.7, BMI 21.8 ± 1.3 kg/m2; six obese age 30.8 ± 8.8 BMI 37.9 ± 6.6 kg/m2) underwent PET-CT imaging of the neck/supraclavicular region using 11C-MRB under RT conditions. The distribution volume ratio (DVR) for 11C-MRB was estimated via multilinear reference tissue model 2 (MRTM2) referenced to the occipital cortex. Two women (one lean and one with obesity) had no detectable BAT. Of the women with detectable BAT, women with obesity had lower 11C-MRB DVR (0.80 ± 0.12 BAT DVR) compared to lean (1.15 ± 0.19 BAT DVR) (p = 0.004). Our findings are consistent with reports that NET is decreased in obesity and suggest that the sympathetic innervation of BAT is altered in obesity.

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Acknowledgements

The authors gratefully acknowledge the participants of the study as well as the nurses and staff at the Yale University PET Center. Funding for this study was supported by Regeneron, Pharmaceuticals, Inc. The funding agency had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the paper. This work was supported by NIH grant 1S10RR029245. This publication was made possible by CTSA Grant Number UL1 TR000142 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

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Correspondence to Janice J. Hwang.

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Sanchez-Rangel, E., Gallezot, J., Yeckel, C.W. et al. Norepinephrine transporter availability in brown fat is reduced in obesity: a human PET study with [11C] MRB. Int J Obes (2019) doi:10.1038/s41366-019-0471-4

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