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β‐Adrenergic receptors control brown adipose UCP‐1 tone and cold response without affecting its circadian rhythmicity
Author(s) -
Razzoli Maria,
Emmett Matthew J.,
Lazar Mitchell A.,
Bartolomucci Alessandro
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800452r
Subject(s) - circadian rhythm , brown adipose tissue , endocrinology , medicine , thermogenin , biology , clock , circadian clock , thermogenesis , receptor , adipose tissue
Brown adipose tissue (BAT) thermogenic functions are primarily mediated by uncoupling protein (UCP)‐ 1. Ucpl gene expression is highly induced by cold temperature, via sympathetic nervous system and β‐adrenergic receptors (β ARs). Ucpl is also repressed by the clock gene Rev‐erba, contributing to its circadian rhythmicity. In this study, we investigated mice lacking β ARs (β‐less mice) to test the relationship between β AR signaling and the BAT molecular clock. We found that in addition to controlling the induction of Ucpl and other key BAT genes at near freezing temperatures, βARs are essential for the basal expression of BAT Ucpl at room temperature. Remarkably, although basal Ucpl expression is low throughout day and night in β‐less mice, the circadian rhythmicity of Ucpl and clock genes in BAT is maintained. Thus, the requirement of βAR signaling for BAT activity is independent of the circadian rhythmicity of Ucpl expression and circadian oscillation of the molecular clock genes. On the other hand, we found that βARs are essential for the normal circadian rhythms of locomotor activity. Our results demonstrate that in addition to controlling the BAT response to extreme cold, βAR signaling is necessary to maintain basal Ucpl tone and to couple BAT circadian rhythmicity to the central clock.—Razzoli, M., Emmett, M. J., Lazar, M. A., Bartolomucci, A. β‐Adrenergic receptors control brown adipose UCP‐1 tone and cold response without affecting its circadian rhythmicity. FASEB J. 32, 5640–5646 (2018). www.fasebj.org