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) receptors. Here we studied the effect of fasting, leptin, and glucose administration on Y(1) receptor gene expression using a transgenic mouse model carrying a mouse Y(1) receptor/LacZ fusion gene. Transgene expression was determined by quantitative analysis of beta-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 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 hyphothalamic, ventromedial, and amygdaloid nuclei. Results suggest that changes in energetic balance affect Y(1) receptor expression in the paraventricular and arcuate nuclei and that leptin regulates the NPY-Y(1) system in the paraventricular nucleus. Different regulatory signals might modulate the NPY-Y(1) transmission in the dorsomedial hyphothalamic and ventromedial hyphothalamic nuclei.
Zammaretti
F
F
Sezione di Farmacologia, Dipartimento di Anatomia, Farmacologia e Medicina Legale, Università di Torino, Via Pietro Giuria 13, 10125 Torino, Italy.
Panzica
G
G
Eva
C
C
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004326:Drinking; D005215:Fasting / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology*; D007031:Hypothalamus / Q000502:physiology*; D007763:Lac Operon / Q000502:physiology; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D054411:Receptors, Leptin; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000502:physiology; D012996:Solutions; D019076:Transgenes / Q000502:physiology
D020738:Leptin; D054411:Receptors, Leptin; D017476:Receptors, Neuropeptide Y; D012996:Solutions; C515447:leptin receptor, mouse; C097212:neuropeptide Y-Y1 receptor; D005947:Glucose