Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-alpha gene products.
We studied temperature homeostasis in male mice lacking all thyroid hormone receptor-alpha gene products (TRalpha-0/0). As other TRalpha-deficient mice, TRalpha-0/0 mice have lower core body temperature (T(C)) than cognate wild-type controls. We found that obligatory thermogenesis is normal in TRalpha-0/0 and that the lower T(C) at room temperature (RT, 20-22 C) is caused by a down setting of the hypothalamic thermostat. However, TRalpha-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 T(4) deiodinase respond normally to cold stimulation, as do serum T(3), serum glycerol (marker of lipolysis), and heart rate. BAT normally contributes to maintain T(C) at RT, 9 C below thermoneutrality, yet TRalpha-0/0 mice do not show signs of being cold stressed at 20-22 C. Instead, oxygen consumption is greater in TRalpha-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 TRalpha is necessary for T(3) to modulate the central control of T(C) 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.
Marrif
Husnia
H
Jewish General Hospital, Division of Endocrinology, 3755 Cote-Ste-Catherine, Montréal, Québec, Canada H3T 1E2.
Schifman
Aria
A
Stepanyan
Zaruhi
Z
Gillis
Marc-Antoine
MA
Calderone
Angelino
A
Weiss
Roy E
RE
Samarut
Jacques
J
Silva
J Enrique
JE
D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000503:physiopathology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature; D003080:Cold Temperature; D005260:Female; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology; D013696:Temperature; D022722:Thermogenesis / Q000187:drug effects; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency*; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000316:Adrenergic alpha-Agonists; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013974:Thyroxine; D009638:Norepinephrine