Bing C, Pickavance L, Wang Q, Frankish H, Trayhurn P, Williams G
Department of Medicine, University of Liverpool, U.K.
Neuroscience. 1997 Sep;80(1):277-84. doi: 10.1016/s0306-4522(97)00121-8.
The fatty Zucker rat has impaired heat production and fails to mount an adequate thermogenic response to cold exposure, partly because of decreased sympathetic drive to thermogenesis in brown adipose tissue. Neuropeptide Y, synthesized in neurons of the hypothalamic arcuate nucleus and released in the paraventricular nucleus, stimulates feeding and inhibits brown adipose tissue activity. The neuropeptide Y neurons are overactive in fatty Zucker rats and are thought to contribute to hyperphagia, reduced energy expenditure and obesity. We have examined the relationship between thermogenic activity in brown adipose tissue (measured as uncoupling protein messenger RNA levels) and hypothalamic neuropeptide Y and neuropeptide Y messenger RNA levels in response to cold exposure (4 degrees C) for 2.5 and 18 h, in fatty and lean Zucker rats. In lean Zucker rats, cold exposure at 4 degrees C for 2.5 and 18 h significantly increased uncoupling protein messenger RNA levels by 3.5-fold (P<0.01) and 3.3-fold (P<0.01), respectively, compared with warm-maintained controls. Exposure to cold for 18 h also increased neuropeptide Y concentrations in the paraventricular nucleus (P<0.01) and ventromedial nucleus (P<0.001) in lean rats, with no change in neuropeptide Y messenger RNA after either 2.5 or 18 h. By contrast, fatty Zucker rats showed no significant changes in uncoupling protein messenger RNA (P>0.05) at either duration of cold exposure. There were also no significant changes in neuropeptide Y levels in any region nor in neuropeptide Y messenger RNA, with cold exposure for either period (P>0.05). In lean rats, cold exposure therefore stimulates brown fat uncoupling protein messenger RNA and also increases neuropeptide Y concentrations in its hypothalamic sites of release. We suggest that increased brown fat thermogenic capacity induced by cold in lean rats may be mediated, at least in part, by decreased neuropeptide Y release in the paraventricular nucleus, resulting in its accumulation in this site. Defective thermogenic responses in fatty rats may result from central dysregulation of brown adipose tissue due to sustained and non-suppressible overactivity of hypothalamic neuropeptide Y neurons.
肥胖型 Zucker 大鼠的产热功能受损，无法对寒冷暴露产生足够的产热反应，部分原因是棕色脂肪组织中交感神经对产热的驱动作用减弱。神经肽 Y 在下丘脑弓状核的神经元中合成，并在室旁核释放，它会刺激进食并抑制棕色脂肪组织的活性。神经肽 Y 神经元在肥胖型 Zucker 大鼠中过度活跃，被认为与食欲亢进、能量消耗减少和肥胖有关。我们研究了肥胖型和瘦型 Zucker 大鼠在 4℃ 寒冷暴露 2.5 小时和 18 小时后，棕色脂肪组织中的产热活性（以解偶联蛋白信使核糖核酸水平衡量）与下丘脑神经肽 Y 及神经肽 Y 信使核糖核酸水平之间的关系。在瘦型 Zucker 大鼠中，与温暖环境下的对照组相比，4℃ 寒冷暴露 2.5 小时和 18 小时后，解偶联蛋白信使核糖核酸水平分别显著增加了 3.5 倍（P<0.01）和 3.3 倍（P<0.01）。在瘦型大鼠中，暴露于寒冷环境 18 小时也会增加室旁核（P<0.01）和腹内侧核（P<0.001）中的神经肽 Y 浓度，而在 2.5 小时或 18 小时后神经肽 Y 信使核糖核酸没有变化。相比之下，肥胖型 Zucker 大鼠在任何一个寒冷暴露时间段内，解偶联蛋白信使核糖核酸水平均无显著变化（P>0.05）。在任何区域，神经肽 Y 水平以及神经肽 Y 信使核糖核酸在两个时间段的寒冷暴露后也均无显著变化（P>0.05）。因此，在瘦型大鼠中，寒冷暴露会刺激棕色脂肪解偶联蛋白信使核糖核酸的产生，同时也会增加其在下丘脑释放部位的神经肽 Y 浓度。我们认为，寒冷在瘦型大鼠中诱导的棕色脂肪产热能力增加可能至少部分是由室旁核中神经肽 Y 释放减少介导的，导致其在该部位积累。肥胖大鼠产热反应缺陷可能是由于下丘脑神经肽 Y 神经元持续且不可抑制的过度活跃导致棕色脂肪组织中枢调节失调所致。
