Assessment of feeding response of tumor-bearing rats to hypothalamic injection and infusion of neuropeptide Y

Assessment of feeding response of tumor-bearing rats to hypothalamic injection and infusion of neuropeptide Y
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DOI:
10.1016/0196-9781(96)00108-8
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发表时间:
1996-01-01
期刊:
影响因子:
3
通讯作者:
Fischer, JE
Fischer, JE
中科院分区:
医学3区
文献类型:
--
作者:
Chance, WT;Balasubramaniam, A;Fischer, JE

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荷瘤大鼠表现出显着减少1至4小时的摄入量的大鼠食物后,下丘脑内注射2微克神经肽Y(NPY)。这种难治性进食反应在厌食症发作之前就存在,并随着厌食症的恶化而变得更加严重。持续输注NPY(125 ng/h)到穹窿周围的TB和对照组大鼠的下丘脑引起增加喂养只有2天。因为层析显示微泵输注10天后NPY是完整的,所以可能发生了NPY受体的下调。每天注射增加剂量的NPY刺激非TB大鼠的ad rib进食,而对TB大鼠没有影响。每天注射肽后对NPY诱导的摄食的脱敏通过对在每天NPY治疗之前增加食物摄入的剂量(500 ng)的NPY的摄食反应的丧失来提示。这些结果表明,下丘脑神经肽Y喂养系统是难治性结核大鼠,甚至在他们表现出厌食症。此外,快速损失的喂养反应发生在大鼠与持续输注NPY到下丘脑组织或每天下丘脑注射的肽,这表明可能的NPY受体介导的改变。因此,通过NPY喂养机制控制肥胖或厌食症可能证明是困难的,因为快速的代偿性受体变化。
Tumor-bearing rats exhibited significant decreases in 1- to 4-h intake of rat chow following the intrahypothalamic injection of 2 mu g neuropeptide Y (NPY). This refractory feeding response was present prior to the onset of anorexia and became more severe as anorexia worsened. The constant infusion of NPY (125 ng/h) into the perifornical hypothalamus of TB and control rats elicited increased feeding for only 2 days. Because chromatography revealed minipump NPY to be intact after 10 infusion days, downregulation of NPY receptors may have occurred. Daily injection of increasing doses of NPY stimulated ad rib feeding in non-TB rats, while having no effect on TB rats. Desensitization to NPY-induced feeding following daily injections of the peptide was suggested by the loss of feeding response to a dose (500 ng) of NPY that increased food intake prior to the daily NPY treatments. These results suggest that hypothalamic NPY feeding systems are refractory in TB rats, even before they exhibit anorexia. In addition, a rapid loss of the feeding response occurred in rats with constant infusion of NPY into hypothalamic tissue or with daily intrahypothalamic injections of the peptide, suggesting possible NPY receptor-mediated alterations. Therefore, control of obesity or anorexia through NPY feeding mechanisms may prove difficult due to rapid compensatory receptor changes.