Chance W T, Balasubramaniam A, Thompson H, Mohapatra B, Ramo J, Fischer J E
Veterans Affairs Medical Center, Cincinnati, OH, USA.
Peptides. 1996;17(5):797-801. doi: 10.1016/0196-9781(96)00108-8.
Tumor-bearing rats exhibited significant decreases in 1- to 4-h intake of rat chow following the intrahypothalamic injection of 2 micrograms 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 lib 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.
给荷瘤大鼠下丘脑内注射2微克神经肽Y（NPY）后，其1至4小时的大鼠饲料摄入量显著减少。这种难治性摄食反应在厌食症发作之前就已出现，并随着厌食症的加重而变得更加严重。向荷瘤大鼠和对照大鼠的穹窿周下丘脑持续输注NPY（125纳克/小时）仅在2天内引起摄食增加。因为色谱分析显示微量泵中的NPY在输注10天后仍保持完整，所以可能发生了NPY受体的下调。每天给非荷瘤大鼠注射递增剂量的NPY可刺激其自由摄食，而对荷瘤大鼠则无影响。每日注射该肽后对NPY诱导的摄食脱敏，这表现为在每日NPY治疗之前能增加食物摄入量的剂量（500纳克）的NPY注射后摄食反应丧失。这些结果表明，即使在荷瘤大鼠出现厌食症之前，其下丘脑NPY摄食系统就已出现难治性。此外，在下丘脑组织中持续输注NPY或每天进行下丘脑内注射的大鼠中，摄食反应迅速丧失，这表明可能存在NPY受体介导的改变。因此，由于受体的快速代偿性变化，通过NPY摄食机制控制肥胖或厌食症可能会很困难。
