Diet-induced obesity in mice overexpressing neuropeptide y in noradrenergic neurons

Abstract

Neuropeptide Y (NPY) is a neurotransmitter associated with feeding and obesity. We have constructed an NPY transgenic mouse model (OE-NPYDBH mouse), where targeted overexpression leads to increased levels of NPY in noradrenergic and adrenergic neurons. We previously showed that these mice become obese on a normal chow. Now we aimed to study the effect of a Western-type diet in OE-NPYDBH and wildtype (WT) mice, and to compare the genotype differences in the development of obesity, insulin resistance, and diabetes. Weight gain, glucose, and insulin tolerance tests, fasted plasma insulin, and cholesterol levels were assayed. We found that female OE-NPYDBH mice gained significantly more weight without hyperphagia or decreased activity, and showed larger white and brown fat depots with no difference in UCP-1 levels. They also displayed impaired glucose tolerance and decreased insulin sensitivity. OE-NPYDBH and WT males gained weight robustly, but no difference in the degree of adiposity was observed. However, 40 of OE-NPYDBH but none of the WT males developed hyperglycaemia while on the diet. The present study shows that female OE-NPYDBH mice were not protected from the obesogenic effect of the diet suggesting that increased NPY release may predispose females to a greater risk of weight gain under high caloric conditions. Copyright © 2012 Suvi T. Ruohonen et al.