Adrenergic stimulation as a means to determine in vivo brown adipose tissue thermogenic capacity

Determination of the capacity for adaptive nonshivering thermogenesis is of importance in a broad range of metabolic studies, including investigations of the effects of cold acclimation, preparation for and arousal from hibernation, diet-induced thermogenesis, and metabolic balance. Adaptive nonshivering thermogenesis is understood as being mediated through the activity of uncoupling-protein-1 (UCP1). Norepinephrine and the β 3 -adrenergic agonist CL-316,423 have long been used to assess the capacity for nonshivering thermogenesis in intact mammals. Here we examine whether in mice ( Mus musculus Linnaeus, 1758) the acclimation-induced thermogenic effect of the β 3 -adrenergic agent CL-316,243 underestimates true adrenergically (norepinephrine-)induced capacity for nonshivering thermogenesis, whether anesthesia partly masks true thermogenic capacity, and to what degree adrenergic responses are proportional to and dependent upon the presence of UCP1. All conditions yielded significant differences between cold- and thermoneutral-acclimated mice and between wild-type and uncoupling protein 1 knockout mice. The cold-acclimation-recruited thermogenesis elicited by CL-316,243 was not statistically significantly lower than that elicited by norepinephrine, and the level of cold acclimation-recruited adrenergically induced thermogenesis was not statistically significantly affected by anesthesia. The absence of UCP1 practically eliminated cold acclimation-recruited adrenergically induced thermogenesis. Cold acclimation-recruited adrenergically-induced thermogenesis is positively associated with UCP1 amount. Qualitatively and quantitatively comparable results are thus obtained irrespective of which adrenergic activator is used.