Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism

Détails

ID Serval
serval:BIB_5F2251955044
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism
Périodique
Molecular and Cellular Endocrinology
Auteur(s)
Raposinho  P. D., Pierroz  D. D., Broqua  P., White  R. B., Pedrazzini  T., Aubert  M. L.
ISSN
0303-7207 (Print)
Statut éditorial
Publié
Date de publication
12/2001
Volume
185
Numéro
1-2
Pages
195-204
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 20
Résumé
Neuropeptide Y (NPY) is involved in the central regulation of appetite, sexual behavior, and reproductive function. We have previously shown that chronic infusion of NPY into the lateral ventricle of normal rats produced an obesity syndrome characterized by hyperphagia, hyperinsulinism and collapse of reproductive function. We further demonstrated that acute inhibition of LH secretion in castrated rats was preferentially mediated by the NPY receptor subtype 5 (Y(5)). In the present study, the effects of chronic, central infusion of NPY, or the mixed Y2-Y5 agonist PYY(3-36), were evaluated both in normal male C57BL/6J mice and Sprague-Dawley rats. After a 7-day infusion to male mice, both NPY and PYY(3-36) at 5 nmol per day, induced marked hyperphagia leading to significant increases in body and fat pad weights. Furthermore, both compounds markedly reduced several markers of the reproductive axis. In the rat study, PYY(3-36) was more active than NPY to inhibit the pituitary-testicular axis, confirming the importance of the Y5 subtype for such effects. In the mouse, chronic NPY infusion induced a sustained increase in corticosterone and insulin secretion. Plasma leptin levels were also markedly increased possibly explaining the observed reduction in gene expression for hypothalamic NPY. Gene expression for hypothalamic POMC was reduced in the NPY- or PYY(3-36)-infused mice, suggesting that NPY exacerbated food intake by both acting through its own receptor(s), and reducing the satiety signal driven by the POMC-derived alpha-MSH. The present study in the mouse suggests in analogy with available rat data, that constant exposure to elevated NPY in the hypothalamic area unabatedly enhances food intake leading to an obesity syndrome including increased adiposity, insulin resistance, hypercorticism, and hypogonadism, reminiscent of the phenotype of the ob/ob mouse, that displays elevated hypothalamic NPY secondary to lack of leptin negative feedback action.
Mots-clé
Animals Hyperphagia/chemically induced/etiology Hypogonadism/chemically induced/etiology Insulin Resistance Lateral Ventricles Leptin/blood Male Mice Mice, Inbred C57BL Neuropeptide Y/administration & dosage/*pharmacology Obesity/*chemically induced/etiology/pathology Peptide YY/administration & dosage/pharmacology Rats Rats, Sprague-Dawley Syndrome
Pubmed
Web of science
Création de la notice
25/01/2008 9:45
Dernière modification de la notice
20/08/2019 15:16
Données d'usage