Abstract
It has been suggested that fibroblast growth factor (FGF)-1 serves as a physiological satiety factor in the hypothalamus, although the molecular mechanism underlying such a function is poorly understood. To gain additional insight 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 (HSP) 27 in the hypothalamus. Whereas FGF-1 expression was restricted to the ependymal cell layer of the cerebral ventricles, HSP27 was more widely expressed in astrocytes residing in the surrounding periventricular region. Similarly, infusion of FGF-1 polypeptide into a lateral ventricle induced dose-dependent HSP27 expression in periventricular astrocytes surrounding the third ventricle, with maximum mRNA levels being attained 6 h after infusion. This induction of HSP27 was accompanied by a significant suppression of feeding behaviour. Interestingly, suppression of feeding caused by intracerebro ventricular infusion of ciliary neurotrophic factor was also accompanied by induction of HSP27 in periventricular astrocytes, but suppression of feeding caused by infusion of leptin was not. It therefore appears that suppression of feeding by FGF-1 is accompanied by selective induction of HSP27 expression in hypothalamic astrocytes surrounding the third ventricle, and that this response may be a key component of the mechanism by which appetite is regulated by FGF-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Appetite / drug effects
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Appetite / genetics*
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Ciliary Neurotrophic Factor / metabolism
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Ciliary Neurotrophic Factor / pharmacology
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Eating / drug effects
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Eating / genetics*
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Ependyma / cytology
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Ependyma / drug effects
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Ependyma / metabolism
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Fibroblast Growth Factor 1
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism*
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Fibroblast Growth Factor 2 / pharmacology
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Gene Expression Regulation / physiology
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Glial Fibrillary Acidic Protein / drug effects
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins
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HSP27 Heat-Shock Proteins
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Heat-Shock Proteins*
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Hypothalamus / cytology
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Hypothalamus / drug effects
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Hypothalamus / metabolism*
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Immunohistochemistry
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Leptin / metabolism
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Leptin / pharmacology
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Luminescent Proteins / genetics
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Male
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Microtubule-Associated Proteins / drug effects
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Microtubule-Associated Proteins / metabolism
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Recombinant Proteins / pharmacology
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Respirovirus / genetics
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Satiety Response / drug effects
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Satiety Response / physiology
Substances
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Ciliary Neurotrophic Factor
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Glial Fibrillary Acidic Protein
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HSP27 Heat-Shock Proteins
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Heat-Shock Proteins
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Hspb1 protein, rat
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Leptin
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Luminescent Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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RNA, Messenger
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Recombinant Proteins
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Fibroblast Growth Factor 2
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Fibroblast Growth Factor 1
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Green Fluorescent Proteins