Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake

Abstract Previous studies have shown that acidic and basic fibroblast growth factor (aFGF and bFGF) and certain fragments of the aFGF N-terminal suppress food intake in rats due to their inhibitory actions on the glucose-sensitive neurons in the lateral hypothalamic area (LHA). The present 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 suppression was also investigated. An injection of anti-FGFR-1 antibody (250 and 350 ng) into the bilateral LHA significantly increased food intake. Synthesized aFGF fragments were infused into the III ventricle to elucidate the structure–activity relationship on the inhibition of feeding. Although aFGF-(1–29) did not affect food intake, [Ser 16 ]aFGF-(1–29) (400 ng) and [Glu 16 ]aFGF-(1–29) (400 ng), in which the cysteine residue at position 16 of aFGF-(1–29) was replaced with structurally similar 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 enhances their inhibitory effects on feeding.