High-fat diet induced adiposity in mice with targeted disruption of the dopamine-3 receptor gene.

Dopamine (DA) signaling has been implicated in the control of energy balance and ingestive behavior. In the present study, we sought to characterize body weight, body fat and food intake regulation in a mouse with a targeted disruption of the dopamine-3 receptor gene (Drd3). In the first set of experiments male and female wild-type and mutant (Drd3-/-) mice were given access to two different diets varying in fat content. Body weight, food intake, carcass analysis and plasma levels of leptin and insulin were measured. Male Drd3-/- mice have increased body weight and body fat when given access to high fat (HF) diet but not standard rodent chow. The female Drd3-/- mice did not demonstrate increased body weight when given access to either diet, but did have increased body fat on both diets. Plasma leptin and insulin levels reflected the increased adiposity demonstrated in each genotype and gender. These findings suggest the D3-R signaling is involved in the regulation of body weight and body fat when mice are given access to diets differing in palatability and fat content.