Prevention of palatable diet-induced hyperphagia in rats by central injection of a VEGFR kinase inhibitor
| Autor: | Anastasia M. Bobilev, Ping Shen, Haini N. Cai, Nuria Waddington Negrao, Audrey Branch |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Taste medicine.medical_specialty Indoles Time Factors medicine.drug_class Hyperphagia Biology Inhibitory postsynaptic potential Tyrosine-kinase inhibitor Rats Sprague-Dawley Eating Food Preferences Behavioral Neuroscience Internal medicine Avoidance Learning medicine Animals Pyrroles Enzyme Inhibitors Overeating Kinase activity Injections Intraventricular Analysis of Variance Kinase Body Weight digestive oral and skin physiology Receptor Protein-Tyrosine Kinases Feeding Behavior Diet Rats Endocrinology Drosophila Analysis of variance Signal transduction |
| Zdroj: | Behavioural Brain Research. 278:506-513 |
| ISSN: | 0166-4328 |
| DOI: | 10.1016/j.bbr.2014.10.004 |
| Popis: | 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 24h 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. |
| Databáze: | OpenAIRE |
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