Fasting, leptin treatment, and glucose administration differentially regulate Y-1 receptor gene expression in the hypothalamus of transgenic mice

NPY is a potent orexigenic signal and represents a key component of targets through which leptin exerts a regulatory restraint on body adiposity. Part of the orexigenic effects of NPY are mediated by hypothalamic NPY-Y-1 rece ptors. Here we studied the effect of fasting, leptin, and glucose administr ation on Y-1 receptor gene expression using a transgenic mouse model carryi ng a mouse Y-1 receptor/LacZ fusion gene. Transgene expression was determin ed by quantitative analysis of beta -galactosidase histochemical staining i n the paraventricular, arcuate, ventromedial, and dorsomedial hypothalamic nuclei and in the medial amygdala, as a control region. Food deprivation for 72 h decreased transgene expression in the paraventric ular nucleus but not in the arcuate nucleus. Leptin treatment, that was per se ineffective, counteracted the decrease of transgene expression induced in the paraventricular nucleus by 72 h fasting. Supplementing the drinking water with 10% glucose increased beta -galactosidase expression both in the paraventricular nucleus and arcuate nucleus of control mice. Finally, none of the treatments altered transgene expression in the dorsomedial hyphotha lamic, ventromedial, and amygdaloid nuclei. Results suggest that changes in energetic balance affect Y-1 receptor expression in the paraventricular an d arcuate nuclei and that leptin regulates the NPY-Y-1 system in the parave ntricular nucleus. Different regulatory signals might modulate the NPY-Y-1 transmission in the dorsomedial hyphothalamic and ventromedial hyphothalami c nuclei.