Nicolaisen 2020 FASEB J
| Nicolaisen TS, Klein AB, Dmytriyeva O, Lund J, Ingerslev LR, Fritzen AM, Carl CS, Lundsgaard AM, Frost M, Ma T, Schjerling P, Gerhart-Hines Z, Flamant F, Gauthier K, Larsen S, Richter EA, Kiens B, Clemmensen C (2020) Thyroid hormone receptor Ξ± in skeletal muscle is essential for T3-mediated increase in energy expenditure. FASEB J 34:15480-91. |
Nicolaisen Trine S, Klein Anders B, Dmytriyeva Oksana, Lund Jens, Ingerslev Lars R, Fritzen Andreas M, Carl Christian S, Lundsgaard Anne-Marie, Frost Mikkel, Ma Tao, Schjerling Peter, Gerhart-Hines Zachary, Flamant Frederic, Gauthier Karine, Larsen Steen, Richter Erik A, Kiens Bente, Clemmensen Christoffer (2020) FASEB J
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 (TRΞ±1) in skeletal muscle, but that T3-mediated elevation in body temperature is achieved in the absence of muscle-TRΞ±1. In slow-twitch soleus muscle, loss-of-function of TRΞ±1 (TRΞ±HSACre) 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 TRΞ±HSACre 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 TRΞ±1 -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. β’ Keywords: Energy expenditure, Energy metabolism, Skeletal muscle, Thyroid hormone β’ Bioblast editor: Plangger M β’ O2k-Network Lab: NO Tromsoe Larsen TS, DK Copenhagen Gerhart-Hines Z, DK Copenhagen Larsen S
Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology
Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS
Pathway: N, NS
HRR: Oxygraph-2k
2020-10
