FIBROBLAST GROWTH-FACTOR RECEPTOR-1 IN THE LATERAL HYPOTHALAMIC AREA REGULATES FOOD-INTAKE

Previous studies have shown that acidic and basic fibroblast growth fa ctor (aFGF and bFGF) and certain fragments of the aFGF N-terminal supp ress food intake in rats due to their inhibitory actions on the glucos e-sensitive neurons in the lateral hypothalamic area (LHA). The presen t study was planned to determine the role of FGF receptor-1 (FGFR-1), which was found in the LHA neurons of rats, on feeding regulation. The structure-activity relationship of aFGF fragments in feeding suppress ion was also investigated. An injection of anti-FGFR-1 antibody (250 a nd 350 ng) into the bilateral LHA significantly increased food intake. Synthesized aFGF fragments were infused into the III ventricle to elu cidate the structure-activity relationship on the inhibition of feedin g. Although aFGF-(1-29) did not affect food intake, [Ser(16)]aFGF-(1-2 9) (400 ng) and [Glu(16)]aFGF-(1-29) (400 ng), in which the cysteine r esidue at position 16 of aFGF-(1-29) was replaced with structurally si milar serine and glutamic acid, were observed to significantly inhibit food intake. These findings suggest that endogenous FGFR-1 in the LHA plays an important role in FGF-induced feeding suppression, while, in addition, the dissolving disulfide bond formation in aFGF fragments e nhances their inhibitory effects on feeding. (C) 1996 Academic Press, Inc.