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Fasting, Leptin Treatment, and Glucose Administration Differentially Regulate Y₁ Receptor Gene Expression in the Hypothalamus of Transgenic Mice

Sezione di Farmacologia, Dipartimento di Anatomia, Farmacologia e Medicina Legale, Università di Torino (F.Z., C.E.), Via Pietro Giuria 13, 10125 Torino, Italy and Sezione di Anatomia, Dipartimento di Anatomia, Farmacologia e Medicina Legale, Università di Torino (G.C.P.), Corso Massimo d’Azeglio, 52, 10126 Torino, Italy

Address all correspondence and requests for reprints to: Prof. Carola Eva, Sezione di Farmacologia, Dipartimento di Anatomia, Farmacologia e Medicina Legale, Via Pietro Giuria, 13, 10125 Torino, Italy. E-mail: carola.eva{at}unito.it

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-Y₁ receptors. Here we studied the effect of fasting, leptin, and glucose administration on Y₁ receptor gene expression using a transgenic mouse model carrying a mouse Y₁ receptor/LacZ fusion gene. Transgene expression was determined by quantitative analysis of ß-galactosidase histochemical staining in 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 paraventricular 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 ß-galactosidase expression both in the paraventricular nucleus and arcuate nucleus of control mice. Finally, none of the treatments altered transgene expression in the dorsomedial hyphothalamic, ventromedial, and amygdaloid nuclei. Results suggest that changes in energetic balance affect Y₁ receptor expression in the paraventricular and arcuate nuclei and that leptin regulates the NPY-Y₁ system in the paraventricular nucleus. Different regulatory signals might modulate the NPY-Y₁ transmission in the dorsomedial hyphothalamic and ventromedial hyphothalamic nuclei.

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