Johann, KorneliaCremer, Anna LenaFischer, Alexander W.Heine, MarkusRial Pensado, EvaResch, JuliaNock, SebastianVirtue, SamuelHarder, LisbethOelkrug, RebeccaAstiz, MarianaBrabant, GeorgWarner, AmyVidal Puig, AntonioOster, HenrikBoelen, AnitaLópez Pérez, Miguel A.Heeren, JoergDalley, Jeffrey W.Backes, HeikoMittag, Jens2020-04-222020-04-222019Johann, K., Cremer, A. L., Fischer, A.W. et al. (2019). Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption. Cell rep, 27, 11, 3385-3400. doi: 10.1016/j.celrep.2019.05.0542211-1247http://hdl.handle.net/10347/21643Regulation of body temperature critically depends on thyroid hormone (TH). Recent studies revealed that TH induces browning of white adipose tissue, possibly contributing to the observed hyperthermia in hyperthyroid patients and potentially providing metabolic benefits. Here, we show that browning by TH requires TH-receptor β and occurs independently of the sympathetic nervous system. The beige fat, however, lacks sufficient adrenergic stimulation and is not metabolically activated despite high levels of uncoupling protein 1 (UCP1). Studies at different environmental temperatures reveal that TH instead causes hyperthermia by actions in skeletal muscle combined with a central body temperature set-point elevation. Consequently, the metabolic and thermogenic effects of systemic hyperthyroidism were maintained in UCP1 knockout mice, demonstrating that neither beige nor brown fat contributes to the TH-induced hyperthermia and elevated glucose consumption, and underlining that the mere presence of UCP1 is insufficient to draw conclusions on the therapeutic potential of browning agentseng© 2019 The Author(s). Open Access. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed. To request permission for a type of use not listed, please contact Elsevier Global Rights Departmenthttps://creativecommons.org/licenses/by-nc-nd/4.0/Brown adipose tissueBeige adipose tissueUncoupling protein 1Thyroid hormone receptorBody temperatureNorepinephrineSympathetic nervous systemMetabolismBeta3-adrenergic receptorPyrexiaHyperthermiaGlucose tolerancejournal article10.1016/j.celrep.2019.05.054open access