|dc.description.abstract||Obesity and excess body fat are the result of caloric intake that exceeds metabolic need, and their development is correlated with insufficient exercise and overeating. Evolutionary pressures tend to promote biological mechanisms which enhance an organism’s ability to obtain nutrients and minimize excessive energy utilization. However, the worldwide trend toward positive energy balance has led to an increased prevalence of obesity. It is a quiet killer, predisposing individuals to a variety of diseases including cardiovascular and metabolic disorders, increasing rates of morbidity and mortality (1). The financial consequences of obesity in terms of medical expenses and loss of productivity has deleterious social costs (2).
In order to understand the mechanisms that promote overeating and obesity at the behavioral level, it is informative to make use of invertebrate and mammalian models of feeding behavior. Using a Drosophila larvae model system, we have demonstrated that norepinephrine-like octopamine (OA) neurons in the fly are acutely required for homeostatic food intake regulation, and selectively enhance intake of sweet, palatable foods. The feeding regulatory effects of OA neurons were determined to dependent on Octβ3R and OAMB receptors, respectively. In addition, we have demonstrated that OA neurons are regulated by a vascular endothelial growth factor receptor (dVegfr, or Pvr), whose activity is required for OA dependent feeding rate increases (3). Based on the homology of the fly OA and norepinephrine systems in mammals, and the similarity of fly dVegfr to mammalian VEGFR2, we hypothesized that VEGF/VEGR2 may have a homologous role mammalian food intake regulation. To investigate this possibility, young rats were treated intracerebroventrically (i.c.v.) with a single dose of VEGFR2 Tyrosine Kinase Inhibitor V (VTKI-V). Treated rats displayed decreased food intake and weight gain. These effects are selectively manifested in different feeding regimens. Animals treated with VTKI-V showed markedly attenuated consumption of palatable food that is sweet and fatty. Meal pattern analysis reveals that this is achieved by consumption of smaller, shorter meals. Overall, our results suggest that VTKI-V treatment may interfere with two separate VEGFR-mediated mechanisms: one which promotes overconsumption of palatable food, and the other mediates body weight gain.||