Transgenic Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

A Novel Model of Increased Adiposity and Impaired Glucose Tolerance

  1. Suvi T. Ruohonen12,
  2. Ullamari Pesonen1,
  3. Niko Moritz3,
  4. Katja Kaipio12,
  5. Matias Röyttä4,
  6. Markku Koulu1 and
  7. Eriika Savontaus15
  1. 1Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
  2. 2Drug Discovery Graduate School, University of Turku, Turku, Finland
  3. 3Department of Orthopedics and Traumatology, University of Turku, Turku, Finland
  4. 4Department of Pathology, University of Turku, Turku, Finland
  5. 5Clinical Pharmacology, TYKSLAB, Health Care District of Southwest Finland, Turku, Finland
  1. Corresponding author: Dr. Eriika Savontaus, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, FI-20014 Turun yliopisto, Finland. E-mail: eriika.savontaus{at}utu.fi

Abstract

OBJECTIVE—A functional polymorphism leucine 7 proline in the human neuropeptide Y (NPY) gene leading to increased NPY release from sympathetic nerves is associated with traits of metabolic syndrome. Although hypothalamic NPY neurons play an established role in promoting positive energy balance, the role of NPY colocalized with norepinephrine in sympathetic nervous system and brain noradrenergic neurons remains obscure.

RESEARCH DESIGN AND METHODS—To clarify the role of NPY in noradrenergic neurons, we generated a transgenic mouse overexpressing NPY under dopamine–β-hydroxylase promoter and characterized the metabolic phenotype of the OE-NPYDβH mouse.

RESULTS—NPY levels are increased by 1.3-fold in adrenal glands and 1.8-fold in the brainstem but not in the hypothalamus in OE-NPYDβH mice. They display increased white adipose tissue mass and cellularity and liver triglyceride accumulation without hyperphagia or increased body weight. Hyperinsulinemia and impaired glucose tolerance develop by the age of 6 months in the OE-NPYDβH mice. Furthermore, circulating ghrelin is significantly increased in comparison with wild-type mice.

CONCLUSIONS—The present study shows that even a moderate increase in NPY levels in noradrenergic neurons leads to disturbances in glucose and lipid metabolism. The OE-NPYDβH mouse is an interesting new model to investigate the pathophysiology of some key components of the cluster of abnormalities characterizing the metabolic syndrome.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 14 February 2008. DOI: 10.2337/db07-0722.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted January 31, 2007.
    • Received May 28, 2007.
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  1. Diabetes vol. 57 no. 6 1517-1525
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