Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption

Kornelia Johann, Anna Lena Cremer, Alexander W Fischer, Markus Heine, Eva Rial Pensado, Julia Resch, Sebastian Nock, Samuel Virtue, Lisbeth Harder, Rebecca Oelkrug, Mariana Astiz, Georg Brabant, Amy Warner, Antonio Vidal-Puig, Henrik Oster, Anita Boelen, Miguel López, Joerg Heeren, Jeffrey W Dalley, Heiko BackesJens Mittag

Abstract

Regulation 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 agents.

Original languageEnglish
JournalCell Reports
Volume27
Issue number11
Pages (from-to)3385-3400.e3
DOIs
Publication statusPublished - 11.06.2019

Fingerprint

Dive into the research topics of 'Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption'. Together they form a unique fingerprint.

Cite this