b-Adrenergic receptors control brown adipose UCP-1 tone and cold response without affecting its circadian rhythmicity

Brown adipose tissue (BAT) thermogenic functions are primarily mediated by uncoupling protein (UCP)-1. Ucp1 gene expression is highly induced by cold temperature, via sympathetic nervous system and b-adrenergic receptors (bARs). Ucp1 is also repressed by the clock gene Rev-erba, contributing to its circadian rhythmicity. In this study, we investigated mice lacking bARs (b-less mice) to test the relationship between bAR signaling and the BAT molecular clock. We found that in addition to controlling the induction of Ucp1 and other key BAT genes at near freezing temperatures, bARs are essential for the basal expression of BAT Ucp1 at room temperature. Remarkably, although basal Ucp1 expression is low throughout day and night in b-less mice, the circadian rhythmicity of Ucp1 and clock genes in BAT is maintained. Thus, the requirement of bAR signaling for BAT activity is independent of the circadian rhythmicity of Ucp1 expression and circadian oscillation of the molecular clock genes. On the other hand, we found that bARs are essential for the normal circadian rhythms of locomotor activity. Our results demonstrate that in addition to controlling the BAT response to extreme cold, bAR signaling is necessary to maintain basal Ucp1 tone and to couple BAT circadian rhythmicity to the central clock.