AAV mediated expression of anti-sense neuropeptide Y cRNA in the arcuate nucleus of rats results in decreased weight gain and food intake
AAV mediated expression of anti-sense neuropeptide Y cRNA in the arcuate nucleus of rats results in decreased weight gain and food intake
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DOI：
10.1016/j.bbrc.2004.12.113
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发表时间：
2005-02-25
影响因子：
3.1
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
Gardiner, JV;Kong, WM;Bloom, SR
神经肽Y（NPY）是脑室内注射给药时最有效的摄食刺激剂。尽管如此，关于它在调节每日食物摄入量和能量平衡方面的重要性，仍有相互矛盾的证据。有人认为，虽然它在对饥饿的反应中很重要，但在调节每日食物摄入量方面作用不大。为探讨神经肽Y（NPY）在摄食调节中的作用，在成年雄性大鼠弓状核中表达了NPY的反义cRNA。最初在体外测试反义NPY（AS-NPY）构建体，与对照相比，反义处理的细胞的NPY释放减少约50%（16.3 +/- 2.0 fmol/L [AS-NPY]对37.3 +/- 7.7 fmol/L [对照]，平均SEM p < 0.05）。注射AAV后第15天和第20天，与对照组相比，反义注射动物下丘脑外植体的NPY释放减少了50%以上（15天42% +/- 6.5% [AS-NPY] vs 100% +/- 36% [对照]，20天41% +/- 6% [AS-NPY] vs 100% +/- 27% [对照]平均SEM，p < 0.05）。在持续50天的研究中，从第16天开始，反义注射动物的体重增加显著降低（第16天：6.25 +/- 1.10 g [AS-NPY]对9.42 +/- 0.65 g [对照]平均SEM，p < 0.05），并保持如此，直到研究结束，此时他们的体重比对照组少约40（第50天：52.0 +/- 9.6 g [AS-NPY]对82.0 +/- 6.3 g [对照]平均SEM，p < 0.01）。从第23天开始，反义注射动物的累积食物摄入量显著降低（第23天：225.8 +/- 1.9 g [AS-NPY] vs 250.6 +/- 8.7 g [对照]，平均SEM，p < 0.05），并保持如此直至研究结束（第50天：834.5 +/-14.8g [AS-NPY]对比926.0 +/-31.7g [对照]，平均SEM，p < 0.05）。类似地，在反义注射的动物中平均每日食物摄入也减少（第7-14天：24.9 +/-0.4g/天[AS-NPY]对27.2 +/-0.4g/天[对照]，平均SEM，p < 0.01）。这些数据支持NPY在调节每日食物摄入以及响应饥饿中的作用。(C)2004年爱思唯尔公司All rights reserved.
Neuropeptide Y (NPY) is the most potent stimulant of feeding when administered by intracerebroventricular injection. Despite this, there is conflicting evidence as to its importance in the regulation of daily food intake and energy balance. It has been suggested that whilst it is important in the response to starvation it has little role in the regulation of daily food intake. To investigate the role of NPY in the regulation of food intake, anti-sense cRNA to NPY was expressed in the arcuate nucleus of adult male rats. The antisense NPY (AS-NPY) construct was initially tested in vitro and there was a decrease of approximately 50% in NPY release from anti-sense treated cells compared to controls (16.3 +/- 2.0 fmol/L [AS-NPY] vs 37.3 +/- 7.7 fmol/L [control], mean SEM p < 0.05). NPY release from hypothalamic explants from anti-sense injected animals was decreased by over 50% compared to those from controls at both 15 and 20 days after AAV injection (15 days 42% +/- 6.5% [AS-NPY] vs 100% +/- 36% [control], 20 days 41% +/- 6% [AS-NPY] vs 100% +/- 27% [control] mean SEM, p < 0.05). In a study lasting for 50 days, weight gain was significantly lower in anti-sense injected animals from day 16 (day 16: 6.25 +/- 1.10 g [AS-NPY] vs 9.42 +/- 0.65 g [control] mean SEM, p < 0.05) and remained so until the end of the study when they had gained approximately 40% less weight than controls (day 50: 52.0 +/- 9.6 g [AS-NPY] vs 82.0 +/- 6.3 g [control] mean SEM, p < 0.01). Cumulative food intake was significantly lower in the anti-sense injected animals from day 23 (day 23: 225.8 +/- 1.9 g [AS-NPY] vs 250.6 +/- 8.7 g [control], mean SEM, p < 0.05) and remained so until the end of the study (day 50: 834.5 +/- 14.8 g [AS-NPY] vs 926.0 +/- 31.7 g [control], mean SEM, p < 0.05). Similarly mean daily food intake was also reduced in the anti-sense injected animals (days 7-14: 24.9 +/- 0.4 g/day [AS-NPY] vs 27.2 +/- 0.4 g/day [control], mean SEM, p < 0.01). These data are supportive of a role for NPY in the regulation of daily food intake as well as in response to starvation. (C) 2004 Elsevier Inc. All rights reserved.