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At thermoneutrality, acute thyroxine-induced thermogenesis and pyrexia are independent of UCP1
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Number of Authors: 42019 (English)In: Molecular Metabolism, ISSN 2212-8778, Vol. 25, p. 20-34Article in journal (Refereed) Published
Abstract [en]

Objective: Hyperthyroidism is associated with increased metabolism (thyroid thermogenesis) and elevated body temperature, often referred to as hyperthermia. Uncoupling protein-1 (UCP1) is the protein responsible for nonshivering thermogenesis in brown adipose tissue. We here examine whether UCP1 is essential for thyroid thermogenesis. Methods: We investigated the significance of UCP1 for thyroid thermogenesis by using UCP1-ablated (UCP1 KO) mice. To avoid confounding factors from cold-induced thermogenesis and to approach human conditions, the experiments were conducted at thermoneutrality, and to resemble conditions of endogenous release, thyroid hormone (thyroxine, T4) was injected peripherally. Results: Both short-term and chronic thyroxine treatment led to a marked increase in metabolism that was largely UCP1-independent. Chronic thyroxine treatment led to a 1-2 degrees C increase in body temperature. This increase was also UCP1 -independent and was maintained even at lower ambient temperatures. Thus, it was pyrexia, i.e. a defended increase in body temperature, not hyperthermia. In wildtype mice, chronic thyroxine treatment induced a large relative increase in the total amounts of UCP1 in the brown adipose tissue (practically no UCP1 in brite/beige adipose tissue), corresponding to an enhanced thermogenic response to norepinephrine injection. The increased UCP1 amount had minimal effects on thyroxine-induced thermogenesis and pyrexia. Conclusions: These results establish that thyroid thermogenesis is a UCP1 -independent process. The fact that the increased metabolism coincides with elevated body temperature and thus with accelerated kinetics accentuates the unsolved issue of the molecular background for thyroid thermogenesis. 

Place, publisher, year, edition, pages
2019. Vol. 25, p. 20-34
Keywords [en]
Thyroid hormone, Thermogenesis, UCP1, Hyperthermia, Pyrexia, Fever, Brown adipose tissue
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-170828DOI: 10.1016/j.molmet.2019.05.005ISI: 000472215300003PubMedID: 31151797OAI: oai:DiVA.org:su-170828DiVA, id: diva2:1339376
Available from: 2019-07-29 Created: 2019-07-29 Last updated: 2019-07-29Bibliographically approved

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Lindsund, ErikCannon, BarbaraNedergaard, Jan
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