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This Article Full Text Full Text (PDF) All Versions of this Article: 583/2/445    most recent jphysiol.2007.133470v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zammaretti, F. Articles by Eva, C. Search for Related Content PubMed PubMed Citation Articles by Zammaretti, F. Articles by Eva, C. Related Collections Integrative

¹ Pharmacology
² Anatomy Section, Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, Italy

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 Y₁ receptor (Y₁R) for neuropeptide Y (NPY) in the dorsomedial (DMH), ventromedial (VMH), arcuate (ARC) and paraventricular (PVN) hypothalamic nuclei of male and female Y₁R/LacZ transgenic mice, carrying the murine Y₁R 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 Y₁R/LacZ transgene expression in the DMH and VMH of male mice whereas no changes were found in the ARC and PVN. Leptin treatment reduced body weight of both MHF diet- and chow-fed male mice but failed to prevent the decrease in Y₁R/LacZ transgene expression apparent in the DMH and VMH of male mice after 8 weeks of MHF diet intake. Conversely, no significant changes of metabolizable energy intake, body weight or hypothalamic β-galactosidase expression were found in MHF diet-fed female Y₁R/LacZ transgenic mice. A gender-related difference of Y₁R/LacZ transgenic mice was also observed in response to leptin treatment that failed to decrease body weight of both MHF diet- and chow-fed female mice. Results herein demonstrate that Y₁R/LacZ FVB mice show a sexual dimorphism both on energy intake and on nucleus-specific regulation of the NPY Y₁R system in the hypothalamus. Overall, these results provide new insights into the mechanism by which diet composition affects the hypothalamic circuit that controls energy homeostasis.

(Received 28 March 2007; accepted after revision 18 June 2007; first published online 21 June 2007)
Corresponding author C. Eva: Sezione di Farmacologia, Dipartimento di Anatomia, Farmacologia e Medicina Legale, Università di Torino, Via P. Giuria, 13-10125 Torino, Italy. Email: carola.eva{at}unito.it

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