Critical roles of nardilysin in the maintenance of body temperature homoeostasis.
Critical roles of nardilysin in the maintenance of body temperature homoeostasis.
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DOI：
10.1038/ncomms4224
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发表时间：
2014
影响因子：
16.6
通讯作者：
Nishi, Eiichiro
中科院分区：
文献类型：
--
作者：
Hiraoka, Yoshinori;Matsuoka, Tatsuhiko;Ohno, Mikiko;Nakamura, Kazuhiro;Saijo, Sayaka;Matsumura, Shigenobu;Nishi, Kiyoto;Sakamoto, Jiro;Chen, Po-Min;Inoue, Kazuo;Fushiki, Tohru;Kita, Toru;Kimura, Takeshi;Nishi, Eiichiro
哺乳动物的体温稳态是通过调节颤抖性和非颤抖性产热以及皮肤血管运动来集中控制的。棕色脂肪组织（BAT）中的非颤抖性产热是由交感神经激活介导的，随后是PGC-1α诱导，其驱动UCP 1。在这里，我们确定nardilysin（Nrd 1和NRDc）作为一个重要的调节体温稳态。Nrd 1 −/−小鼠由于增强的BAT产热和多动而显示出增加的能量消耗。尽管有这些发现，Nrd 1 −/−小鼠表现出体温过低和冷耐受不良，这归因于体温设定点降低，绝缘不良和冷诱导产热受损。β3肾上腺素能受体、PGC-1α和UCP 1对寒冷的反应在缺乏NRDc的情况下严重受损。在分子水平上，NRDc和PGC-1α相互作用并共定位于UCP 1增强子，NRDc在此抑制PGC-1α活性。这些发现揭示了NRDc的一种新的核功能，并为温度调节机制提供了重要的见解。 哺乳动物体温的精确调节对生存很重要。在这里，作者表明，肽酶nardilysin抑制转录因子PGC-1α，并确定nardilysin作为基础体温，冷诱导产热和身体绝缘的调节剂。
Body temperature homoeostasis in mammals is governed centrally through the regulation of shivering and non-shivering thermogenesis and cutaneous vasomotion. Non-shivering thermogenesis in brown adipose tissue (BAT) is mediated by sympathetic activation, followed by PGC-1α induction, which drives UCP1. Here we identify nardilysin (Nrd1 and NRDc) as a critical regulator of body temperature homoeostasis. Nrd1−/− mice show increased energy expenditure owing to enhanced BAT thermogenesis and hyperactivity. Despite these findings, Nrd1−/− mice show hypothermia and cold intolerance that are attributed to the lowered set point of body temperature, poor insulation and impaired cold-induced thermogenesis. Induction of β3-adrenergic receptor, PGC-1α and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1α interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1α activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation. The precise regulation of mammalian body temperature is important for survival. Here the authors show that the peptidase nardilysin represses the transcription factor PGC-1α, and identify nardilysin as a regulator of basal body temperature, cold-induced thermogenesis and body insulation.
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影响因子：
64.8
作者：
Enerback, S;Jacobsson, A;Kozak, LP
通讯作者：
Kozak, LP
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
64.5
作者：
Lin, JD;Wu, PH;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
4.1
作者：
Hospital, V;Chesneau, V;Prat, A
通讯作者：
Prat, A
影响因子：
29
作者：
Feldmann, Helena M.;Golozoubova, Valeria;Nedergaard, Jan
通讯作者：
Nedergaard, Jan