title: Sex-dependent regulation of hypothalamic neuropeptide Y-Y1 receptor gene expression in leptin treated obese (ob/ob) or lean mice.
abstract: Pharmacological and genetic studies have shown that the Y1receptor (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 (1μg/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.
authors.affiliation: Department of Neuroscience, University of Turin, C.so Massimo d'Azeglio 52, Torino, Italy; Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mele
authors.affiliation: Department of Neuroscience, University of Turin, C.so Massimo d'Azeglio 52, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zammaretti
authors.affiliation: Department of Neuroscience, University of Turin, C.so Massimo d'Azeglio 52, Torino, Italy; Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Longo
authors.affiliation: Department of Neuroscience, University of Turin, C.so Massimo d'Azeglio 52, Torino, Italy; Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Panzica
authors.affiliation: Department of Neuroscience, University of Turin, C.so Massimo d'Azeglio 52, Torino, Italy; Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Oberto
authors.affiliation: Department of Neuroscience, University of Turin, C.so Massimo d'Azeglio 52, Torino, Italy; Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), Regione Gonzole 10, 10043 Orbassano, Torino, Italy. Electronic address: carola.eva@unito.it.
authors.forename: Carola
authors.initials: C
authors.lastname: Eva
keywords: Hypothalamus; Leptin; NPY; Sex; Y(1) receptor; ob/ob mice