title: Neuropeptide Y in the noradrenergic neurones induces obesity and inhibits sympathetic tone in mice.
abstract: OBJECTIVE
  Neuropeptide Y (NPY) co-localized with noradrenaline in central and sympathetic nervous systems seems to play a role in the control of energy metabolism. In this study, the aim was to elucidate the effects and pathophysiological mechanisms of increased NPY in catecholaminergic neurones on accumulation of body adiposity.
  
  
  METHODS
  Transgenic mice overexpressing NPY under the dopamine-beta-hydroxylase promoter (OE-NPY(DβH) ) and wild-type control mice were followed for body weight gain and body fat content. Food intake, energy expenditure, physical activity, body temperature, serum lipid content and markers of glucose homoeostasis were monitored. Thermogenic and lipolytic responses in adipose tissues, and urine catecholamine and tissue catecholamine synthesizing enzyme levels were analysed as indices of sympathetic tone.
  
  
  RESULTS
  Homozygous OE-NPY(DβH) mice showed significant obesity accompanied with impaired glucose tolerance and insulin resistance. Increased adiposity was explained by neither increased food intake or fat absorption nor by decreased total energy expenditure or physical activity. Adipocyte hypertrophy and decreased circulating lipid levels suggested decreased lipolysis and increased lipid uptake. Brown adipose tissue thermogenic capacity was decreased and brown adipocytes filled with lipids. Enhanced response to adrenergic stimuli, downregulation of catecholamine synthesizing enzyme expressions in the brainstem and lower adrenaline excretion supported the notion of low basal catecholaminergic activity.
  
  
  CONCLUSIONS
  Increased NPY in catecholaminergic neurones induces obesity that seems to be a result of preferential fat storage. These results support the role of NPY as a direct effector in peripheral tissues and an inhibitor of sympathetic activity in the pathogenesis of obesity.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; Drug Research Doctoral Program, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland.
authors.forename: L H
authors.initials: LH
authors.lastname: Vähätalo
authors.forename: S T
authors.initials: ST
authors.lastname: Ruohonen
authors.forename: S
authors.initials: S
authors.lastname: Mäkelä
authors.forename: M
authors.initials: M
authors.lastname: Kovalainen
authors.forename: A
authors.initials: A
authors.lastname: Huotari
authors.forename: K A
authors.initials: KA
authors.lastname: Mäkelä
authors.forename: J A
authors.initials: JA
authors.lastname: Määttä
authors.forename: I
authors.initials: I
authors.lastname: Miinalainen
authors.forename: R
authors.initials: R
authors.lastname: Gilsbach
authors.forename: L
authors.initials: L
authors.lastname: Hein
authors.forename: L
authors.initials: L
authors.lastname: Ailanen
authors.forename: M
authors.initials: M
authors.lastname: Mattila
authors.forename: K
authors.initials: K
authors.lastname: Eerola
authors.forename: M
authors.initials: M
authors.lastname: Röyttä
authors.forename: S
authors.initials: S
authors.lastname: Ruohonen
authors.forename: K-H
authors.initials: KH
authors.lastname: Herzig
authors.forename: E
authors.initials: E
authors.lastname: Savontaus
mesh_terms: D002001:Adipose Tissue, Brown; D059331:Adrenergic Neurons / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D009478:Neuropeptide Y; D012333:RNA, Messenger
keywords: adipose tissue; glucose tolerance; mice; neuropeptide Y; obesity; sympathetic nervous system