Kalra P S, Dube M G, Xu B, Kalra S P
Department of Physiology, University of Florida College of Medicine, Gainesville 32610-0274, USA.
Regul Pept. 1997 Oct 31;72(2-3):121-30. doi: 10.1016/s0167-0115(97)01045-8.
Disruption of neural signaling by microinjection of a neurotoxin, colchicine (COL), in the ventromedial hypothalamus (VMH) of rats results in rapid and transient hyperphagia and body weight gain. Since neuropeptide Y (NPY) is a potent hypothalamic orexigenic signal and continuous NPY receptor activation by intracerebroventricular (icv) NPY infusion results in hyperphagia and obesity, we tested the hypothesis that altered NPYergic signaling may underlie the transient hyperphagia in COL-injected rats. Immediately following COL (4 microg) microinjections in the ventromedial nucleus (VMN) rats displayed hyperphagia both during the lights-on and lights-off periods. Concomitant with hyperphagia, preproNPY mRNA levels in the arcuate nucleus and NPY levels in the paraventricular nucleus decreased in a time-dependent manner. However, food intake in response to intracerebroventricular injections of NPY (29, 117 and 470 pmole) was significantly higher in COL-injected rats and the latency to initiation of feeding was markedly reduced as compared to controls. The smallest dose of NPY which was virtually ineffective in control rats, evoked near maximal intake in COL-injected rats. This enhanced response lasted for only 4 days paralleling the transient hyperphagia. The NPY Y1 receptor antagonist 1229U91 (5 or 30 microg/rat, icv) significantly suppressed feeding in COL-treated rats thereby indicating that hyperphagia in these rats was dependent upon endogenous NPY. Overall, these studies demonstrate that not only high levels, but low levels of NPY may also result in hyperphagia and increased body weight and this hyperphagia may be attributed to the rapid development of NPY Y1 receptor hypersensitivity.
向大鼠腹内侧下丘脑（VMH）微量注射神经毒素秋水仙碱（COL）会破坏神经信号，导致大鼠迅速且短暂地出现摄食亢进和体重增加。由于神经肽Y（NPY）是一种强大的下丘脑促食欲信号，通过脑室内（icv）注入NPY持续激活NPY受体会导致摄食亢进和肥胖，因此我们检验了这样一个假设，即NPY能信号改变可能是COL注射大鼠出现短暂摄食亢进的基础。在腹内侧核（VMN）微量注射COL（4微克）后，大鼠在光照期和黑暗期均表现出摄食亢进。与摄食亢进同时出现的是，弓状核中前NPY原mRNA水平和室旁核中NPY水平呈时间依赖性下降。然而，与对照组相比，COL注射大鼠对脑室内注射NPY（29、117和470皮摩尔）的食物摄入量显著更高，且开始进食的潜伏期明显缩短。在对照大鼠中几乎无效的最小剂量NPY，在COL注射大鼠中却引发了接近最大摄入量的反应。这种增强的反应仅持续4天，与短暂的摄食亢进平行。NPY Y1受体拮抗剂1229U91（5或30微克/大鼠，icv）显著抑制了COL处理大鼠的进食，从而表明这些大鼠的摄食亢进依赖于内源性NPY。总体而言，这些研究表明，不仅高水平的NPY，低水平的NPY也可能导致摄食亢进和体重增加，这种摄食亢进可能归因于NPY Y1受体超敏反应的快速发展。
