Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-α gene products

Husnia Marrif, Aria Schifman, Zaruhi Stepanyan, Marc Antoine Gillis, Angelino Calderone, Roy E Weiss, Jacques Samarut, J. Enrique Silva

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44 Scopus citations

Abstract

We studied temperature homeostasis in male mice lacking all thyroid hormone receptor-α gene products (TRα-0/0). As other TRα-deficient mice, TRα-0/0 mice have lower core body temperature (TC) than cognate wild-type controls. We found that obligatory thermogenesis is normal in TRα-0/0 and that the lower TC at room temperature (RT, 20-22 C) is caused by a down setting of the hypothalamic thermostat. However, TRα-0/0 mice are cold intolerant due to impaired facultative thermogenesis. Norepinephrine-induced brown adipose tissue (BAT) thermogenesis is blunted, even though BAT-relevant genes and T4 deiodinase respond normally to cold stimulation, as do serum T3, serum glycerol (marker of lipolysis), and heart rate. BAT normally contributes to maintain T C at RT, 9 C below thermoneutrality, yet TRα-0/0 mice do not show signs of being cold stressed at 20-22 C. Instead, oxygen consumption is greater in TRα-0/0 than in wild-type mice at RT, suggesting the recruitment of an alternate, cold-activated form of thermogenesis to compensate for the lack of BAT thermogenesis. These results indicate that TRα is necessary for T3 to modulate the central control of TC and for an essential step in norepinephrine activation of BAT thermogenesis but not to sustain obligatory thermogenesis. In addition, the results provide evidence for an alternate form of facultative thermogenesis, which probably originates in skeletal muscle and that is less effective and more energy demanding than BAT thermogenesis.

Original languageEnglish (US)
Pages (from-to)2872-2884
Number of pages13
JournalEndocrinology
Volume146
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Marrif, H., Schifman, A., Stepanyan, Z., Gillis, M. A., Calderone, A., Weiss, R. E., Samarut, J., & Silva, J. E. (2005). Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-α gene products. Endocrinology, 146(7), 2872-2884. https://doi.org/10.1210/en.2004-1544