Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3
Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3
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DOI：
10.1152/ajpendo.00615.2013
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发表时间：
2014-03-01
影响因子：
5.1
通讯作者：
Reitman, Marc L.
中科院分区：
文献类型：
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作者：
Lateef, Dalya M.;Abreu-Vieira, Gustavo;Reitman, Marc L.
蛙皮素受体亚型-3（BRS-3）调节能量稳态，Brs 3敲除（Brs 3（-/y））小鼠是低代谢的、体温过低的和摄食过多的并且发展肥胖。我们现在报告，如果将体温作为身体活动水平和亮/暗相的函数进行分析，则更容易检测到体温降低。体力活动水平与4 min后体温的相关性最好。Brs 3（-/y）代谢表型不是由于固有受损的棕色脂肪组织功能或从大脑到棕色脂肪组织的交感神经信号的通信，因为Brs 3（-/y）小鼠对应激、急性冷暴露和β 3-肾上腺素能激活具有完整的产热反应，并且Brs 3（-/y）小鼠更喜欢较冷的环境。用BRS-3激动剂MK-5046处理增加了野生型但不是Brs 3（-/y）小鼠的棕色脂肪组织温度和体温。下丘脑内输注MK 5046可升高体温。这些数据表明BRS-3对体温的调节是通过交感传出神经上游的中枢机制进行的。Brs 3（-/y）小鼠的体温降低是由于能量稳态调节的改变影响了体温的更高中心调节，而不是棕色脂肪组织的内在缺陷。
Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, with Brs3 knockout (Brs3(-/y)) mice being hypometabolic, hypothermic, and hyperphagic and developing obesity. We now report that the reduced body temperature is more readily detected if body temperature is analyzed as a function of physical activity level and light/dark phase. Physical activity level correlated best with body temperature 4 min later. The Brs3(-/y) metabolic phenotype is not due to intrinsically impaired brown adipose tissue function or in the communication of sympathetic signals from the brain to brown adipose tissue, since Brs3(-/y) mice have intact thermogenic responses to stress, acute cold exposure, and beta 3-adrenergic activation, and Brs3(-/y) mice prefer a cooler environment. Treatment with the BRS-3 agonist MK-5046 increased brown adipose tissue temperature and body temperature in wild-type but not Brs3(-/y) mice. Intrahypothalamic infusion of MK5046 increased body temperature. These data indicate that the BRS-3 regulation of body temperature is via a central mechanism, upstream of sympathetic efferents. The reduced body temperature in Brs3(-/y) mice is due to altered regulation of energy homeostasis affecting higher center regulation of body temperature, rather than an intrinsic defect in brown adipose tissue.