Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota, USA; and.
Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
FASEB J. 2018 Oct;32(10):5640-5646. doi: 10.1096/fj.201800452R. Epub 2018 May 1.
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 β-adrenergic receptors (βARs). Ucp1 is also repressed by the clock gene Rev-erbα, contributing to its circadian rhythmicity. In this study, we investigated mice lacking βARs (β-less mice) to test the relationship between βAR 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, βARs are essential for the basal expression of BAT Ucp1 at room temperature. Remarkably, although basal Ucp1 expression is low throughout day and night in β-less mice, the circadian rhythmicity of Ucp1 and clock genes in BAT is maintained. Thus, the requirement of βAR 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 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 Ucp1 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.
棕色脂肪组织（BAT）的产热功能主要由解偶联蛋白（UCP）-1 介导。Ucp1 基因的表达受冷温度的高度诱导，通过交感神经系统和β-肾上腺素能受体（βARs）。Ucp1 也被时钟基因 Rev-erbα 抑制，有助于其昼夜节律性。在这项研究中，我们研究了缺乏βARs 的小鼠（β-less 小鼠），以测试βAR 信号与 BAT 分子钟之间的关系。我们发现，除了控制 Ucp1 和其他关键 BAT 基因在接近冰点温度下的诱导外，βARs 对室温下 BAT Ucp1 的基础表达也是必不可少的。值得注意的是，尽管β-less 小鼠中 Ucp1 的基础表达在白天和黑夜都很低，但 BAT 中 Ucp1 和时钟基因的昼夜节律性仍然保持。因此，βAR 信号对 BAT 活性的要求与 Ucp1 表达的昼夜节律性和分子钟基因的昼夜振荡无关。另一方面，我们发现βARs 对运动活动的正常昼夜节律是必需的。我们的结果表明，除了控制 BAT 对极冷的反应外，βAR 信号还需要维持基础 Ucp1 音调和将 BAT 昼夜节律性与中央时钟联系起来。-Razzoli，M.，Emmett，M. J.，Lazar，M. A.，Bartolomucci，A.β-肾上腺素能受体控制棕色脂肪 UCP-1 音调和冷反应，而不影响其昼夜节律性。
