Frankish H M, Dryden S, Wang Q, Bing C, MacFarlane I A, Williams G
Department of Medicine, University of Liverpool, UK.
Brain Res. 1995 Oct 2;694(1-2):139-46. doi: 10.1016/0006-8993(95)00834-d.
Neuropeptide Y (NPY) is synthesized in arcuate (ARC) neurons which project principally to the paraventricular nucleus (PVN). NPY injected into the PVN causes hyperphagia, reduced energy expenditure and eventually obesity, effects which are opposed by nicotine. We aimed to investigate whether nicotine's effects on energy balance might be mediated by inhibition of hypothalamic NPYergic neurons. Nicotine or saline was given for 1 or 12 days using osmotic minipumps, and additional groups of rats were food-restricted to the intake of the nicotine-treated groups to allow for the effects of hypophagia on hypothalamic NPY. One day's nicotine treatment (12 mg/kg/day) reduced food intake by 30% (P < 0.001) and body weight by 2% (P < 0.01 vs. controls). NPY mRNA levels were significantly reduced by 40% (P < 0.05) and NPY concentrations fell significantly by 33% in the ARC and PVN (both P < 0.01). Matched food restriction also reduced NPY levels significantly in the ARC and PVN (P < 0.02 vs. controls) but had no effect on NPY mRNA. 12 days' nicotine treatment (12 mg/kg/day) lowered cumulative food intake by 8% (P = 0.02) and body weight by 10% (P < 0.05). NPY mRNA levels rose by 40% (P < 0.05), while NPY levels again fell in the ARC and PVN (both P < 0.05). Food restriction, which induced weight loss comparable with that during nicotine treatment, increased NPY mRNA to levels that were 100% above controls (P < 0.01) and also significantly higher than in the nicotine-treated group (P < 0.05). Food restriction also reduced NPY peptide levels in the PVN (P < 0.02), but did not affect those in the ARC. In addition, 12 days' nicotine treatment significantly reduced plasma insulin levels compared with controls (P < 0.05). We suggest that nicotine may inhibit NPY synthesis in the hypothalamus, independently of any effects due to altered energy balance. Reduced activity of NPYergic neurons in the ARC-PVN projection may mediate the effects of nicotine on energy balance.
神经肽Y（NPY）在主要投射至室旁核（PVN）的弓状核（ARC）神经元中合成。向PVN注射NPY会导致食欲亢进、能量消耗减少并最终引发肥胖，而尼古丁则会产生相反的作用。我们旨在研究尼古丁对能量平衡的影响是否可能通过抑制下丘脑NPY能神经元来介导。使用渗透微型泵给予尼古丁或生理盐水1天或12天，另外几组大鼠进行食物限制，使其摄入量与尼古丁处理组相同，以考虑摄食减少对下丘脑NPY的影响。尼古丁处理1天（12毫克/千克/天）使食物摄入量减少30%（P<0.001），体重减少2%（与对照组相比，P<0.01）。ARC和PVN中的NPY mRNA水平显著降低40%（P<0.05），NPY浓度显著下降33%（两者P<0.01）。相匹配的食物限制也使ARC和PVN中的NPY水平显著降低（与对照组相比，P<0.02），但对NPY mRNA没有影响。尼古丁处理12天（12毫克/千克/天）使累积食物摄入量降低8%（P=0.02），体重降低10%（P<0.05）。NPY mRNA水平升高40%（P<0.05），而ARC和PVN中的NPY水平再次下降（两者P<0.05）。导致体重减轻程度与尼古丁处理期间相当的食物限制使NPY mRNA升高至比对照组高100%的水平（P<0.01），且也显著高于尼古丁处理组（P<0.05）。食物限制还降低了PVN中的NPY肽水平（P<0.02），但对ARC中的水平没有影响。此外，与对照组相比，尼古丁处理12天显著降低了血浆胰岛素水平（P<0.05）。我们认为，尼古丁可能独立于能量平衡改变所产生的任何影响，抑制下丘脑NPY的合成。ARC-PVN投射中NPY能神经元活性降低可能介导了尼古丁对能量平衡的影响。
