IL-15 receptor deletion results in circadian changes of locomotor and metabolic activity.
IL-15 receptor deletion results in circadian changes of locomotor and metabolic activity.
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DOI：
10.1007/s12031-009-9319-z
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Pan W
中科院分区：
文献类型：
--
作者：
He Y;Wu X;Khan RS;Kastin AJ;Cornelissen-Guillaume GG;Hsuchou H;Robert B;Halberg F;Pan W
白细胞介素-15 （IL-15）是一种在正常大脑中产生的细胞因子，作用于其特异性受体IL-15Rα和神经元细胞中的共受体IL-2Rβ和IL-2Rγ。然而，大脑IL-15系统的功能尚不清楚。为了验证IL-15Rα调节代谢活性和体温的假设，我们量化了IL-15Rα敲除小鼠的特异性代谢表型。这些看起来正常的老鼠更瘦，脂肪含量更低。在整个昼夜周期中，敲除小鼠在运动活动和散热方面具有显著更高的肢相。在光照期，有更多的食物摄入、氧气消耗和二氧化碳产生。这表明IL-15Rα参与了昼夜节律调节。光期较高的耗氧量表明敲除小鼠的适应性产热。受体敲除小鼠的体温在光照期明显高于对照组，这主要是由于0600和0900 h之间发生了很大的差异。除了代谢室研究和昼夜节律分析外，下丘脑匀浆的qPCR显示，食欲素和瞬时受体电位香兰素4阳离子通道的mRNA表达更高。与IL-15Rα在下丘脑中的直接作用一致，IL-15处理野生型小鼠在视前区诱导c-Fos表达。我们得出结论，IL-15激活小鼠下丘脑神经元有助于体温调节并改变代谢表型。
Interleukin-15 (IL-15) is a cytokine produced in the normal brain that acts on its specific receptor IL-15Rα and co-receptors IL-2Rβ and IL-2Rγ in neuronal cells. The functions of the cerebral IL-15 system, however, are not yet clear. To test the hypothesis that IL-15Rα regulates metabolic activity and body temperature, we quantified the specific metabolic phenotype of IL-15Rα knockout mice. These normal-appearing mice were leaner with lower fat composition. During the entire circadian cycle, the knockout mice had a significantly higher acrophase in locomotor activity and heat dissipation. During the light phase, there was significantly greater food intake, oxygen consumption, and carbon dioxide production. The difference in the dark and light phases suggests that IL-15Rα participates in circadian rhythm regulation. The higher oxygen consumption in the light phase indicates adaptive thermogenesis in the knockout mice. The body temperature of the receptor knockout mice was significantly higher than the control in the light phase, and this was mainly caused by a large difference occurring between 0600 and 0900 h. In addition to the metabolic chamber studies and circadian rhythm analyses, qPCR of hypothalamic homogenates indicated higher mRNA expression of orexin and transient receptor potential vanilloid 4 cation channels. Consistent with a direct role of IL-15Rα in the hypothalamus, IL-15 treatment of the wild-type mice induced c-Fos expression in the preoptic area. We conclude that activation of hypothalamic neurons by IL-15 in mice contributes to thermoregulation and modifies the metabolic phenotype.
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影响因子：
9.8
作者：
DeRuisseau, LR;Parsons, AD;Overton, JM
通讯作者：
Overton, JM
影响因子：
4.8
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Pan, Weihong;Hsuchou, Hung;Kastin, Abba J.
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Kastin, Abba J.
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4.8
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Pan, Weihong;Hsuchou, Hung;Kastin, Abba J.
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Kastin, Abba J.
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2.9
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Monda, M;Viggiano, A;De Luca, V
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De Luca, V
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4.7
作者：
Pan, W.;Hsuchou, H.;Kastin, A. J.
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Kastin, A. J.