Selvais P L, Labuche C, Nguyen X N, Ketelslegers J M, Denef J F, Maiter D M
Unite de Diabétologie et Nutrition and Unité d'Histologie, University of Louvain Medical School, Brussels, Belgium.
J Neuroendocrinol. 1997 Jan;9(1):55-62. doi: 10.1046/j.1365-2826.1997.00566.x.
Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food intake in rodents. To elucidate the mechanisms for these effects, we studied the hypothalamic content, synthesis, and distribution of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar rats, three weeks of zinc-deprivation consistently induced a reduction and a cyclic pattern of night- and day-time food intake, as well as of water intake. This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair-fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100 +/- 8, ZD: 61 +/- 4, PF: 78 +/- 2 arbitrary densitometric units, ADU, P < 0.01) and an increase of hypothalamic NPY (CTR: 100 +/- 11, ZD: 154 +/- 10, PF: 126 +/- 4 ADU, P < 0.05), without peptide modification. The two neuropeptidergic systems were not affected by the cycles of feeding, with the exception of the NPY-immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract), that was inversely correlated to the food intake in both ZD and PF animals. In a second experiment, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY synthesis was observed in ZD rats, suggesting that the increase observed in Wistar is adaptative rather than instrumental to the abnormal food intake. In conclusion, we have further characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and shown in these animals a decreased activity of the GAL system and an increased activity of the NPY system, likely corresponding to a compensatory response of the two neuropeptidergic systems, as observed in food-deprived animals. As spontaneous food intake of ZD rats does not increase, a resistance to NPY could also be present. These behavioural and neuropeptidergic changes were partially reversed by reintroduction of zinc in the diet. In Zucker rats, the same behaviour occurred despite an insensitivity of the NPY system to the zinc-deficiency. In addition, we describe a nutritional regulation of the NPY-immunoreactivity in the geniculo-hypothalamic tract, that could constitute the substrate of circadian rhythm modulation by timed feeding.
饮食中锌缺乏会导致啮齿动物的食物摄入量显著减少并呈现周期性模式。为了阐明这些影响的机制，我们研究了大鼠在锌缺乏和重新喂食期间下丘脑内甘丙肽（GAL）和神经肽Y（NPY）的含量、合成及分布情况。在Wistar大鼠中，三周的锌缺乏持续导致昼夜食物摄入量以及饮水量的减少和周期性模式。锌缺乏（ZD）大鼠以及程度较轻的配对喂食（PF）大鼠出现这种情况的同时，下丘脑GAL mRNA浓度降低（对照组：100±8，ZD组：61±4，PF组：78±2任意光密度单位，ADU，P<0.01），而下丘脑NPY增加（对照组：100±11，ZD组：154±10，PF组：126±4 ADU，P<0.05），且肽未发生修饰。除了视交叉上核（膝状体 - 下丘脑束）中的NPY免疫反应性外，这两个神经肽系统不受进食周期的影响，在ZD和PF动物中，其与食物摄入量呈负相关。在第二个实验中，我们表明4天的锌补充抑制了两周锌缺乏诱导的行为，并逆转了ZD动物中NPY mRNA的增加。我们最终证明锌缺乏在Zucker大鼠中诱导了类似的行为。然而，在这些NPY合成组成性上调的大鼠中，ZD大鼠未观察到NPY合成的变化，这表明在Wistar大鼠中观察到的增加是适应性的，而非导致异常食物摄入的直接原因。总之，我们进一步描述了锌缺乏的Wistar大鼠的周期性进食行为，并表明在这些动物中GAL系统活性降低，NPY系统活性增加，这可能对应于两个神经肽系统的代偿反应，正如在饥饿动物中观察到的那样。由于ZD大鼠的自发食物摄入量未增加，可能也存在对NPY的抵抗。饮食中重新添加锌后，这些行为和神经肽变化部分得到逆转。在Zucker大鼠中，尽管NPY系统对锌缺乏不敏感，但仍出现相同的行为。此外，我们描述了膝状体 - 下丘脑束中NPY免疫反应性的营养调节，这可能构成定时进食对昼夜节律调节的基础。
