Transgenic mice overexpressing neuropeptide Y in noradrenergic neurons: a novel model of increased adiposity and impaired glucose tolerance.
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.


METHODS
To clarify the role of NPY in noradrenergic neurons, we generated a transgenic mouse overexpressing NPY under dopamine-beta-hydroxylase promoter and characterized the metabolic phenotype of the OE-NPY(DbetaH) 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-NPY(DbetaH) 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-NPY(DbetaH) 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-NPY(DbetaH) mouse is an interesting new model to investigate the pathophysiology of some key components of the cluster of abnormalities characterizing the metabolic syndrome.
Ruohonen
Suvi T
ST
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Pesonen
Ullamari
U
Moritz
Niko
N
Kaipio
Katja
K
Röyttä
Matias
M
Koulu
Markku
M
Savontaus
Eriika
E
D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000502:physiology; D004247:DNA / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D005838:Genotype; D054439:Ghrelin / Q000378:metabolism; D018149:Glucose Intolerance / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D054439:Ghrelin; D009478:Neuropeptide Y; D004247:DNA; D004299:Dopamine beta-Hydroxylase