Pharmacological and genetic studies have shown that the Y1 receptor (Y1R) 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 Y1R gene expression in the hypothalamus of lean and obese Y1R/LacZ transgenic mice (TgY1R/LacZ) carrying the murine Y1R promoter linked to the LacZ gene that induces the expression of β-galactosidase. Two daily intraperitoneal injections with leptin (1 μg/g of body weight for one week) of male and female lean (TgY1R/LacZ+/+) and obese (TgY1R/LacZob/ob) mice induced a significant decrease of body weight in both sexes and genotypes. In males, leptin administration decreased β-galactosidase activity in the PVN and DMH of lean mice, and increased transgene expression in the same hypothalamic nuclei of obese mice. Sex-related differences were also observed in both genotypes, since leptin treatment failed to affect transgene expression in hypothalamus of lean and obese female mice. These results provide further evidence for a sexual dimorphism of the hypothalamic NPY-Y1R-mediated pathway in response to changes in leptin circulating levels.

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

MELE, PAOLO;LONGO, ANGELA;PANZICA, Giancarlo;OBERTO, Alessandra;EVA, Carola Eugenia
Last
2016

Abstract

Pharmacological and genetic studies have shown that the Y1 receptor (Y1R) 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 Y1R gene expression in the hypothalamus of lean and obese Y1R/LacZ transgenic mice (TgY1R/LacZ) carrying the murine Y1R promoter linked to the LacZ gene that induces the expression of β-galactosidase. Two daily intraperitoneal injections with leptin (1 μg/g of body weight for one week) of male and female lean (TgY1R/LacZ+/+) and obese (TgY1R/LacZob/ob) mice induced a significant decrease of body weight in both sexes and genotypes. In males, leptin administration decreased β-galactosidase activity in the PVN and DMH of lean mice, and increased transgene expression in the same hypothalamic nuclei of obese mice. Sex-related differences were also observed in both genotypes, since leptin treatment failed to affect transgene expression in hypothalamus of lean and obese female mice. These results provide further evidence for a sexual dimorphism of the hypothalamic NPY-Y1R-mediated pathway in response to changes in leptin circulating levels.
1649
Pt A
102
109
www.elsevier.com/locate/bri
Hypothalamus; Leptin; NPY; ob/ob mice; Sex; Y1 receptor; Neuroscience (all); Molecular Biology; Developmental Biology; Neurology (clinical)
Mele, Paolo; Zammaretti, Francesca; Longo, Angela; Panzica, Giancarlo; Oberto, Alessandra; Eva, Carola
File in questo prodotto:
File Dimensione Formato  
2016MeleBR.pdf

Accesso riservato

Descrizione: 2016Mele Brain res
Tipo di file: PDF EDITORIALE
Dimensione 2.53 MB
Formato Adobe PDF
2.53 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
MeleBrainResarch_4aperto.pdf

Accesso aperto

Descrizione: Mele BR AperTO
Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 740.56 kB
Formato Adobe PDF
740.56 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1593194
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact