Mohammed K Hankir1, Mathias Kranz2, Susanne Keipert3, Juliane Weiner4, Sille G Andreasen1, Matthias Kern1, Marianne Patt5, Nora Klöting1, John T Heiker4, Peter Brust2, Swen Hesse1,5, Martin Jastroch3, Wiebke K Fenske6. 1. Integrated Research and Treatment Centre for Adiposity Diseases, Department of Medicine, University of Leipzig, Leipzig, Germany. 2. Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Helmholtz Centre Dresden-Rossendorf, Leipzig, Germany. 3. Helmholtz Diabetes Center, Helmholtz Center Munich, Neuherburg, Germany. 4. Collaborative Research Center for Obesity Mechanisms, University of Leipzig, Leipzig, Germany; and. 5. Department of Nuclear Medicine, Leipzig University Hospital, Leipzig, Germany. 6. Integrated Research and Treatment Centre for Adiposity Diseases, Department of Medicine, University of Leipzig, Leipzig, Germany WiebkeKristin.Fenske@medizin.uni-leipzig.de.
Abstract
18F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy-3H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18F-FDG uptake independently of UCP1 thermogenic function.
18F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods:UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy-3H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18F-FDG uptake independently of UCP1 thermogenic function.
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