Thyroid hormone is a major regulator of thermogenesis, acting both in peripheral 
organs and on central autonomic pathways. Mice heterozygous for a point mutation 
in thyroid hormone receptor α1 display increased thermogenesis as a consequence 
of high sympathetic brown fat stimulation. Surprisingly, despite the 
hypermetabolism, their body temperature is not elevated. Here we show, using 
isolated tail arteries, that defective thyroid hormone receptor α1 signaling 
impairs acetylcholine-mediated vascular relaxation as well as 
phenylephrine-induced vasoconstriction. Using infrared thermography on conscious 
animals, we demonstrate that these defects severely interfere with appropriate 
peripheral heat conservation and dissipation, which in turn leads to 
compensatory alterations in brown fat activity. Consequently, when the 
vasoconstrictive defect in mice heterozygous for a point mutation in thyroid 
hormone receptor α1 was reversed with the selective α1-adrenergic agonist 
midodrine, the inappropriate heat loss over their tail surface was reduced, 
normalizing brown fat activity and energy expenditure. Our analyses demonstrate 
that thyroid hormone plays a key role in vascular heat conservation and 
dissipation processes, adding a unique aspect to its well-documented functions 
in thermoregulation. The data thus facilitate understanding of temperature 
hypersensitivity in patients with thyroid disorders. Moreover, the previously 
unrecognized connection between cardiovascular regulation and metabolic activity 
revealed in this study challenges the interpretation of several experimental 
paradigms and questions some of the currently derived hypotheses on the role of 
thyroid hormone in thermogenesis.