Feeding suppression by fibroblast growth factor-1 is accompanied by selective induction of heat shock protein 27 in hypothalamic astrocytes

If has been suggested that fibroblast growth factor (FGF)-1 serves as a phy siological satiety factor in the hypothalamus, although the molecular mecha nism underlying such a function is poorly understood. To gain additional in sight into this issue, we used a Sendai virus (SeV) gene expression system in rats to explore genes differentially expressed subsequent to expression of FGF-1. Using cDNA arrays, we determined that infusion of FGF-1/SeV into one lateral ventricle induced selective expression of heat shock protein (H SP) 27 in the hypothalamus. Whereas FGF-1 expression was restricted to the ependymal cell layer of the cerebral ventricles, HSP27 was more widely expr essed in astrocytes residing in the surrounding periventricular region. Sim ilarly, infusion of FGF-1 polypeptide into a lateral ventricle induced dose -dependent HSP27 expression in periventricular astrocytes surrounding the t hird ventricle, with maximum mRNA levels being attained 6 h after infusion. This induction of HSP27 was accompanied by a significant suppression of fe eding behaviour. Interestingly, suppression of feeding caused by intracereb roventricular infusion of ciliary neurotrophic factor was also accompanied by induction of HSP27 in periventricular astrocytes, but suppression of fee ding caused by infusion of leptin was not. It therefore appears that suppre ssion of feeding by FGF-1 is accompanied by selective induction of HSP27 ex pression in hypothalamic astrocytes surrounding the third ventricle, and th at this response may be a key component of the mechanism by which appetite is regulated by FGF-1.