Research reportPrevention of palatable diet-induced hyperphagia in rats by central injection of a VEGFR kinase inhibitor

- One i.c.v. dose of a VEGFR tyrosine kinase inhibitor blockedoverconsumption of sweet/fatty food.
- The attenuated intake isdue toconsumption of smaller, shorter meals.
- Treatment alsocaused decreased body weight gain in rats fed with CHOW or palatable food.
- Effects of a single injection on intake and body weight are rapid and persistent over five days.
- The VEGFR pathway may provide therapeutic targets for prevention of diet induced overeating.

Our previous studies have demonstrated a critical role of a VEGFR-like signaling pathway in hunger-driven overeating of sugar-rich food in Drosophila larvae. In the current study, we investigate whether the VEGFR signaling mechanism plays a similar role in the feeding behavior of vertebrates using male Sprague Dawley rats. Young rats were treated intracerebroventrically (i.c.v.) with a single dose (2 μg) of VEGFR2 Tyrosine Kinase Inhibitor V (VTKI-V), an N-cyclopropylnaphthamide compound that selectively inhibits the kinase activity of VEGFR2 at subnanomolar concentrations. We find that animals treated with VTKI-V showed markedly attenuated overconsumption of palatable food that is sweet and fatty. The subsequent meal pattern analysis reveals that is achieved by consumption of smaller, shorter meals. Furthermore, i.c.v. injection of VTKI-V decreased body weight gain in animals fed with CHOW or palatable food. These inhibitory effects of the drug were detectable within 24 h and persisted for at least five days. Given that body weight was affected by the drug regardless of diet while food intake was selectively altered in palatable diet fed animals, these results raise the possibility that i.c.v. injection of VTKI-V may interfere the functions of two separate VEGFR-mediated mechanisms: one promotes overconsumption of palatable food, and the other mediates body weight gain.