Fever responses of Zucker rats with and without fatty mutation of the leptin receptor
Fever responses of Zucker rats with and without fatty mutation of the leptin receptor
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DOI：
10.1152/ajpregu.00376.2001
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发表时间：
2002-01-01
影响因子：
2.8
通讯作者：
Romanovsky, AA
中科院分区：
文献类型：
--
作者：
Ivanov, AI;Romanovsky, AA
瘦素被认为参与从外周到大脑的发热信号传导。 Zucker肥胖大鼠的瘦素受体基因存在所谓的脂肪突变，并表达一种功能失调的蛋白质。比较肥胖大鼠 (fa/fa) 和瘦大鼠 (Fa/Fa 和 Fa/fa) 的发烧反应的研究得出了矛盾的结果。为了解决这些矛盾，我们评估了在热中性（29℃）和凉爽环境（20℃）下脂肪突变对感染性和应激相关发烧的影响。扎克 fa/fa 和 Fa/？通过颈静脉导管向大鼠输注大肠杆菌脂多糖（LPS；10 微克/千克）（感染性热），或通过导管输注生理盐水（对照），或接受疼痛性肌肉注射生理盐水（应激热）。在热中性条件下，肥胖大鼠对所有测试刺激的结肠温度（T-c）反应与瘦大鼠的反应没有差异。在凉爽的环境中，肥胖大鼠对所有刺激的 Tc 反应均比瘦大鼠低 0.5 ℃。 Zucker 脂肪大鼠在寒冷中观察到的 LPS 诱导和应激相关发热的减弱与文献数据一致，文献数据表明这些大鼠的棕色脂肪组织（主要产热效应器）在形态和功能上存在缺陷。脂肪 Zucker 大鼠在热中性条件下对致热刺激的正常发热反应表明，脂肪突变不会中断从外周到大脑的发热信号传导。
Leptin is thought to be involved in febrigenic signaling from the periphery to the brain. Zucker obese rats have a so-called fatty mutation in the leptin receptor gene and express a dysfunctional protein. Studies comparing the fever responses of fatty (fa/fa) rats and of their lean (Fa/Fa and Fa/fa) counterparts yield contradictory results. To resolve these contradictions, we evaluated the effect of fatty mutation on infectious and stress-associated fevers at thermoneutrality (29 degreesC) and in a cool environment (20 degreesC). Zucker fa/fa and Fa/? rats were infused with Escherichia coli lipopolysaccharide (LPS; 10 mug/kg) through a jugular catheter (infectious fever) or with saline through the catheter (control) or received a painful intramuscular injection of saline (stress fever). At thermoneutrality, the colonic temperature (T-c) responses of fatty rats to all stimuli tested were no different from the responses of lean rats. In a cool environment, Tc responses of fatty rats to all stimuli were similar to0.5 degreesC lower than those of lean rats. The observed attenuation of LPS-induced and stress-associated fevers in Zucker fatty rats in the cold agrees with the literature data showing that brown adipose tissue (the major heat production effector) is morphologically and functionally defective in these rats. The normal febrile responses of fatty Zucker rats to pyrogenic stimuli at thermoneutrality indicate that fatty mutation does not interrupt febrigenic signaling from the periphery to the brain.