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 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, [Ser16]aFGF-(1-29) (400 ng) and [Glu16]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.
Li
A J
AJ
Department of Physiology, Faculty of Medicine, Kyushu University, Kukuoka 812-82, Japan.
Oomura
Y
Y
Hori
T
T
Aou
S
S
Sasaki
K
K
Kimura
H
H
Tooyama
I
I
D000595:Amino Acid Sequence; D000818:Animals; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000502:physiology*
D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors