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 co-localized 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-beta-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 six months in the OE-NPYDβH mice. Furthermore, circulating ghrelin is significantly increased in comparison with wildtype mice