CYCLIC FEEDING-BEHAVIOR AND CHANGES IN HYPOTHALAMIC GALANIN AND NEUROPEPTIDE-Y GENE-EXPRESSION INDUCED BY ZINC-DEFICIENCY IN THE RAT

Dietary zinc-deficiency induces a striking reduction and a cyclic patt ern of food intake in rodents. To elucidate the mechanisms for these e ffects, we studied the hypothalamic content, synthesis, and distributi on of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency an d refeeding in the rat. In Wistar rats, three weeks of zinc-deprivatio n 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. T he two neuropeptidergic systems were not affected by the cycles of fee ding, with the exception of the NPY-immunoreactivity in the suprachias matic nuclei (geniculo-hypothalamic tract), that was inversely correla ted to the food intake in both ZD and PF animals. In a second experime nt, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of N PY mRNA in ZD animals. We finally demonstrated that zinc-deficiency in duced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY syn thesis 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 feedin g behaviour of the zinc-deficient Wistar rats, and shown in these anim als a decreased activity of the GAL system and an increased activity o f the NPY system, likely corresponding to a compensatory response of t he 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 n utritional regulation of the NPY-immunoreactivity in the geniculo-hypo thalamic tract, that could constitute the substrate of circadian rhyth m modulation by timed feeding.