title: The neuropeptide Y Y1 receptor regulates leptin-mediated control of energy homeostasis and reproductive functions.
abstract: The orexigenic neurotransmitter neuropeptide Y (NPY) plays a central role in the hypothalamic control of food intake and energy balance. NPY also exerts an inhibition of the gonadotrope axis that could be important in the response to poor metabolic conditions. In contrast, leptin provides an anorexigenic signal to centrally control the body needs in energy. Moreover, leptin contributes to preserve adequate reproductive functions by stimulating the activity of the gonadotrope axis. It is of interest that hypothalamic NPY represents a primary target of leptin actions. To evaluate the importance of the NPY Y1 and Y5 receptors in the downstream pathways modulated by leptin and controlling energy metabolism as well as the activity of the gonadotrope axis, we studied the effects of leptin administration on food intake and reproductive functions in mice deficient for the expression of either the Y1 or the Y5 receptor. Furthermore, the role of the Y1 receptor in leptin resistance was determined in leptin-deficient ob/ob mice bearing a null mutation in the NPY Y1 locus. Results point to a crucial role for the NPY Y1 receptor in mediating the NPY pathways situated downstream of leptin actions and controlling food intake, the onset of puberty, and the maintenance of reproductive functions.
authors.affiliation: Division of Endocrinology, Diabetology and Metabolism, University of Lausanne Medical School, CH-1011 Lausanne, Switzerland. Francois.Pralong@chuv.hospvd.ch
authors.forename: François P
authors.initials: FP
authors.lastname: Pralong
authors.forename: Christine
authors.initials: C
authors.lastname: Gonzales
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Voirol
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: Hans-R
authors.initials: HR
authors.lastname: Brunner
authors.forename: Rolf C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: Josiane
authors.initials: J
authors.lastname: Seydoux
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
mesh_terms: D000483:Alleles; D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D004734:Energy Metabolism; D005215:Fasting; D005260:Female; D006706:Homeostasis; D006963:Hyperphagia / Q000209:etiology; D007700:Kinetics; D020738:Leptin / Q000235:genetics / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D054411:Receptors, Leptin; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D012741:Sexual Maturation
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D017476:Receptors, Neuropeptide Y; C515447:leptin receptor, mouse; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; D007986:Luteinizing Hormone