Mice lacking brain-type creatine kinase activity show defective thermoregulation.
Mice lacking brain-type creatine kinase activity show defective thermoregulation.
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DOI：
10.1016/j.physbeh.2009.02.003
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发表时间：
2009-04-20
影响因子：
2.9
通讯作者：
Van der Zee, Catharina E. E. M.
中科院分区：
文献类型：
--
作者：
Streijger, Femke;Pluk, Helma;Oerlemans, Frank;Beckers, Gaby;Bianco, Antonio C.;Ribeiro, Miriam O.;Wieringa, Be;Van der Zee, Catharina E. E. M.
关键词：
细胞质脑型肌酸激酶和线粒体普遍存在的肌酸激酶（CK-B 和 UbCKmit）在哺乳动物生命的青春期前和成年期表达。这些肌酸激酶 (CK) 亚型存在于整个中枢和周围神经系统的神经细胞类型以及含有平滑肌的组织中，它们在细胞能量稳态中发挥着重要作用。在这里，我们报告了小鼠中 CK 活性与体温节律和适应性体温调节的耦合。由于两种脑型 CK 异构体均不存在，因此在每日周期的每个早晨（不活动）期间，体温会重复性地低于正常值约 1.0°C。由于 CK−−/−− 小鼠在 24 小时寒冷暴露期间会出现严重的体温过低，因此兼性非颤抖生热作用也会受到损害。有人认为与脂肪代谢有关，因为 CK−−/−− 小鼠与野生型对照小鼠的比较显示，体重增加减少与白色和棕色脂肪积累较少以及棕色脂肪细胞较小相关。此外，葡萄糖、甘油三酯和瘦素的循环水平也会降低。然而，广泛的生理测试和解偶联蛋白1分析表明，产热问题并不是由于棕色脂肪细胞的异常反应引起的，因为去甲肾上腺素输注会导致体温正常升高。此外，我们证明早晨气温的周期性下降也与运动减少、食物摄入减少或麻木敏感性增加等节律改变无关。尽管当大脑中缺乏 CK 时，一些整体功能会发生改变，但综合研究结果表明，低效的神经元传递是温度调节缺陷的主要因素。
The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~1.0°C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK−−/−− mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK−−/−− mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect.
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影响因子：
9.8
作者：
Kuiper JW;Pluk H;Oerlemans F;van Leeuwen FN;de Lange F;Fransen J;Wieringa B
通讯作者：
Wieringa B
影响因子：
56.9
作者：
Conti, Bruno;Sanchez-Alavez, Manuel;Bartfai, Tamas
通讯作者：
Bartfai, Tamas
DOI：
10.1086/physzool.52.2.30152564
发表时间：
1979-01-01
期刊：
PHYSIOLOGICAL ZOOLOGY
影响因子：
--
作者：
HUDSON, JW;SCOTT, IM
通讯作者：
SCOTT, IM
影响因子：
4.3
作者：
DEKOK, YJM;GEURDS, MPA;WIERINGA, B
通讯作者：
WIERINGA, B
影响因子：
4.7
作者：
in 't Zandt, HJA;Renema, WKJ;Heerschap, A
通讯作者：
Heerschap, A