Sex-dependent regulation of hypothalamic neuropeptide Y-Y1 receptor gene expression in leptin treated obese (ob/ob) or lean mice.

Pharmacological and genetic studies have shown that the Y receptor (YR) for Neuropeptide Y (NPY) plays a crucial role in the control of feeding behavior under metabolic conditions of low leptin levels or leptin deficiency. In this study, we investigated the effect of leptin deficiency and leptin replacement on YR gene expression in the hypothalamus of lean and obese YR/LacZ transgenic mice (TgYR/LacZ) carrying the murine Y1R promoter linked to the LacZ gene that induces the expression of β-galactosidase. Two daily intraperitoneal injections with leptin (1μg/g of body weight for one week) of male and female lean (TgYR/LacZ) and obese (TgYR/LacZ) mice induced a significant decrease of body weight in both sexes and genotypes.

Sex-dependent regulation of hypothalamic neuropeptide Y-Y1 receptor gene expression in moderate/high fat, high-energy diet-fed mice.

In this study we investigated whether long-term consumption of a moderate/high fat (MHF), high-energy diet can affect the gene expression of the Y(1) receptor (Y(1)R) for neuropeptide Y (NPY) in the dorsomedial (DMH), ventromedial (VMH), arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei of male and female Y(1)R/LacZ transgenic mice, carrying the murine Y(1)R promoter linked to the LacZ gene. MHF diet-fed male mice showed an increased consumption of metabolizable energy that was associated with a significant increase in body weight as compared with chow-fed controls. In parallel, consumption of a MHF diet for 8 weeks significantly decreased Y(1)R/LacZ transgene expression in the DMH and VMH of male mice whereas no changes were found in the ARC and PVN.

Evidence of altered neuropeptide Y content and neuropeptide Y1 receptor gene expression in the hypothalamus of pregnant transgenic mice.

Alterations in the density of neuropeptide Y (NPY)-immunoreactive fibers and of NPY1 receptor gene expression in the hypothalamus of Y1R/LacZ transgenic pregnant mice were investigated. In the paraventricular nucleus of mice on the 18th d of pregnancy NPY immunoreactivity was significantly decreased, and NPY1 receptor gene expression, as measured by histochemical staining of beta-galactosidase and in situ hybridization of NPY1 receptor mRNA, was significantly increased compared with those in estrous mice. Conversely, pregnant transgenic mice displayed a significant induction of NPY immunoreactivity and a reduction of NPY1 receptor gene expression in the ventromedial nucleus.

Increased expression of the neuropeptide Y receptor Y(1) gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone.

The neurosteroid allopregnanolone, a reduced metabolite of progesterone, induces anxiolytic effects by enhancing GABA(A) receptor function. Neuropeptide Y (NPY) and GABA are thought to interact functionally in the amygdala, and this interaction may be important in the regulation of anxiety. By using Y(1)R/LacZ transgenic mice, which harbour a fusion construct comprising the promoter of the mouse gene for the Y(1) receptor for NPY linked to the lacZ gene, we previously showed that long-term treatment with benzodiazepine receptor ligands modulates Y(1) receptor gene expression in the medial amygdala.

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.