Cold-sensing TRPM8 channel participates in circadian control of the brown adipose tissue
Cold-sensing TRPM8 channel participates in circadian control of the brown adipose tissue
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DOI：
10.1016/j.bbamcr.2017.09.011
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发表时间：
2017-12-01
影响因子：
5.1
通讯作者：
de Lauro Castrucci, Ana Maria
中科院分区：
文献类型：
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作者：
Moraes, Maria Nathalia;Monteiro de Assis, Leonardo Vinicius;de Lauro Castrucci, Ana Maria
瞬时受体电位（TRP）通道是已知的调节能量代谢，TRPM 8已成为一个有趣的球员在这方面。在这里，我们证明了冷传感器TRPM 8在棕色脂肪组织（BAT）的时钟基因和时钟控制基因的调节中的作用。我们研究了TrpM 8在眼睛、视交叉上核和BAT中的时间分布;只有BAT显示了TrpM 8转录本的时间变化。来自缺乏TRPM 8的小鼠的眼睛在LD周期中失去了Peri的时间分布。与野生型动物（WT）相比，眼部昼夜生理学的这种改变可以解释响应于光脉冲的自发活动的开始延迟。与WT或TrpVl KO小鼠相比，来自TrpM 8 KO小鼠的棕色脂肪细胞表现出更大的多室性。此外，与WT小鼠相比，TrpM 8 KO小鼠中Ucpl和UCPl表达显著降低。关于昼夜节律成分，Perl、Per 2、Bmall、Pparalpha和Pparjl的表达在保持在LD中的WT小鼠中振荡，而在不存在TRPM 8的情况下，时钟基因的表达在幅度上降低并且缺乏时间振荡。因此，我们的研究结果揭示了TRPM 8通道的新作用：它参与眼睛和BAT中的时钟和时钟控制基因的调节，以及BAT产热。由于生物钟机制的破坏与许多代谢紊乱相关，TRPM 8通道的药理学调节可能成为一个有前途的治疗靶点，通过增加产热、能量消耗和生物钟基因激活来平衡体重增加。
Transient receptor potential (TRP) channels are known to regulate energy metabolism, and TRPM8 has become an interesting player in this context. Here we demonstrate the role of the cold sensor TRPM8 in the regulation of clock gene and clock controlled genes in brown adipose tissue (BAT). We investigated TrpM8 temporal profile in the eyes, suprachiasmatic nucleus and BAT; only BAT showed temporal variation of TrpM8 transcripts. Eyes from mice lacking TRPM8 lost the temporal profile of Peri in LD cycle. This alteration in the ocular circadian physiology may explain the delay in the onset of locomotor activity in response to light pulse, as compared to wild type animals (WT). Brown adipocytes from TrpM8 KO mice exhibited a larger multilocularity in comparison to WT or TrpVl KO mice. In addition, Ucpl and UCP1 expression was significantly reduced in TrpM8 KO mice in comparison to WT mice. Regarding circadian components, the expression of Perl, Per2, Bmall, Ppar alpha, and Pparjl oscillated in WT mice kept in LD, whereas in the absence of TRPM8 the expression of clock genes was reduced in amplitude and lack temporal oscillation. Thus, our results reveal new roles for TRPM8 channel: it participates in the regulation of clock and clock-controlled genes in the eyes and BAT, and in BAT thermogenesis. Since disruption of the clock machinery has been associated with many metabolic disorders, the pharmacological modulation of TRPM8 channel may become a promising therapeutic target to counterbalance weight gain, through increased thermogenesis, energy expenditure, and clock gene activation.