title: Prevention of palatable diet-induced hyperphagia in rats by central injection of a VEGFR kinase inhibitor.
abstract: 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.
authors.affiliation: Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Branch
authors.affiliation: Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Bobilev
authors.affiliation: Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA.
authors.forename: Nuria Waddington
authors.initials: NW
authors.lastname: Negrao
authors.affiliation: Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA.
authors.forename: Haini
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA. Electronic address: pshen@uga.edu.
authors.forename: Ping
authors.initials: P
authors.lastname: Shen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004032:Diet / Q000009:adverse effects*; D004330:Drosophila; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005247:Feeding Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D006963:Hyperphagia / Q000209:etiology* / Q000517:prevention & control*; D007211:Indoles; D007276:Injections, Intraventricular; D008297:Male; D011758:Pyrroles; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013649:Taste / Q000187:drug effects; D013997:Time Factors
chemical_list: C517608:3-((2,4-dimethyl-3-(ethoxycarbonyl)pyrrol-5-yl)methylidenyl)indolin-2-one; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D020794:Receptor Protein-Tyrosine Kinases
keywords: Body weight; Food intake; Hyperphagia; Meal pattern; Palatable diet; VEGF/VEGFR