University: University of Leipzig, Helmholtz Centre Dresden-Rossendorf
Authors: Mohammed K. Hankir, Mathias Kranz, Susanne Keipert, Juliane Weiner, Sille G. Andreasen, Matthias Kern, Marianne Patt, Nora Klöting, John T. Heiker, Peter Brust, Swen Hesse, Martin Jastroch and Wiebke K. Fenske
Journal: Journal of Nuclear Medicine
Impact Factor: 7.887 (What is the IF?).
TITLE: Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1–Deficient Mice
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.
In human PET imaging studies, brown adipose tissue (BAT) 18F-FDG uptake has been shown to be markedly increased by controlled cold exposure and agonism of β3 adrenergic receptors, correlating positively with changes in energy expenditure.
Similar findings have been made in small-animal PET imaging studies performed on mice. Mitochondrial uncoupling protein 1 (UCP1) endows both human and mouse brown adipocytes with thermogenic capacity. It is widely assumed that BAT 18F-FDG uptake provides an indirect quantitative measure of thermogenesis.
We therefore sought to formally test this basic assumption by performing 18F-FDG PET/MRI experiments on UCP1-deficient mice that exhibit defective BAT thermogenesis and uncoupled respiration in response to the selective β3 adrenergic receptor agonist CL 316, 243