Thyroid hormone receptor α in skeletal muscle is essential for T3-mediated increase in energy expenditure

Trine Sand Nicolaisen, Anders Bue Klein, Oksana Dmytriyeva, Jens Lund, Lars Roed Ingerslev, Andreas Mæchel Fritzen, Christian Strini Carl, Annemarie Lundsgaard, Mikkel Frost, Tao Ma, Peter Schjerling, Zachary Gerhart-Hines, Frederic Flamant, Karine Gauthier, Steen Larsen, Erik A. Richter, Bente Kiens, Christoffer Clemmensen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

22 Citationer (Scopus)
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Abstract

Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole-body energy metabolism and body temperature has not been resolved. Here, we show that T3-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα1 ) in skeletal muscle, but that T3-mediated elevation in body temperature is achieved in the absence of muscle-TRα1 . In slow-twitch soleus muscle, loss-of-function of TRα1 (TRαHSACre ) alters the fiber-type composition toward a more oxidative phenotype. The change in fiber-type composition, however, does not influence the running capacity or motivation to run. RNA-sequencing of soleus muscle from WT mice and TRαHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TRα1-linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3-stimulated increase in whole-body energy expenditure.

OriginalsprogEngelsk
TidsskriftF A S E B Journal
Vol/bind34
Udgave nummer11
Sider (fra-til)15480-15491
Antal sider12
ISSN0892-6638
DOI
StatusUdgivet - 2020

Bibliografisk note

CURIS 2020 NEXS 317

Emneord

  • Det Natur- og Biovidenskabelige Fakultet

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