Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure

Ruy A. Louzada, Maria C.S. Santos, João Paulo A. Cavalcanti-de-Albuquerque, Igor F. Rangel, Andrea C.F. Ferreira, Antonio Galina, Joao Pedro S. Werneck-de-Castro, Denise P. Carvalho

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


During cold acclimation, shivering is progressively replaced by nonshivering thermogenesis. Brown adipose tissue (BAT) and skeletal muscle are relevant for nonshivering thermogenesis, which depends largely on thyroid hormone. Since the skeletal muscle fibers progressively adapt to cold exposure through poorly defined mechanisms, our intent was to determine whether skeletal muscle type 2 deiodinase (D2) induction could be implicated in the long-term skeletal muscle cold acclimation. We demonstrate that in the red oxidative soleus muscle, D2 activity increased 2.3-fold after 3 days at 4°C together with the brown adipose tissue D2 activity, which increased 10-fold. Soleus muscle and BAT D2 activities returned to the control levels after 10 days of cold exposure, when an increase of 2.8-fold in D2 activity was detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers. Propranolol did not prevent muscle D2 induction, but it impaired the decrease of D2 in BAT and soleus after 10 days at 4°C. Cold exposure is accompanied by increased oxygen consumption, UCP3, and PGC-1a genes expression in skeletal muscles, which were partialy prevented by propranolol in soleus and gastrocnemius. Serum total and free T3 is increased during cold exposure in rats, even after 10 days, when BAT D2 is already normalized, suggesting that skeletal muscle D2 activity contributes significantly to circulating T3 under this adaptive condition. In conclusion, cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation.

Original languageEnglish (US)
Pages (from-to)E1020-E1029
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number11
StatePublished - Dec 1 2014
Externally publishedYes


  • Cold acclimation
  • Deiodinase
  • Skeletal muscle
  • Thermogenesis
  • Thyroid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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