title: Neuropeptide Y in noradrenergic neurons induces obesity in transgenic mouse models.
abstract: Neuropeptide Y (NPY) in noradrenergic neurons plays an important role in modulating the release and effects of catecholamines in a prolonged stress response. Among other functions, it controls energy metabolism. Transgenic expression of Npy in noradrenergic neurons in mice allowed showing that it is critical for diet- and stress-induced gain in fat mass. When overexpressed, NPY in noradrenergic neurons increases adiposity in gene-dose-dependent fashion, and leads to metabolic disorders such as impaired glucose tolerance. However, the mechanisms of obesity seem to be different in mice heterozygous and homozygous for the Npy transgene. While in heterozygous mice the adipogenic effect of NPY is important, in homozygous mice inhibition of sympathetic tone leading to decreased lipolytic activity and impaired brown fat function, as well as increased endocannabinoid levels contribute to obesity. The mouse model provides novel insight to the mechanisms of human diseases with increased NPY due to chronic stress or gain-of-function gene variants, and a tool for development of novel therapeutics.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Vähätalo
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
authors.forename: Suvi T
authors.initials: ST
authors.lastname: Ruohonen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland; Drug Research Doctoral Program, University of Turku, Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Ailanen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland; Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland. Electronic address: eriika.savontaus@utu.fi.
authors.forename: Eriika
authors.initials: E
authors.lastname: Savontaus
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y
keywords: Endocannabinoid system; Glucose metabolism; Hepatosteatosis; Lipid metabolism; Metabolic disorder; Neuropeptide Y; Obesity