Abstract
Transgenic expression in the hypothalamus of syndecan-1, a cell surface heparan sulfate proteoglycan (HSPG) and modulator of ligand-receptor encounters, produces mice with hyperphagia and maturity-onset obesity resembling mice with reduced action of alpha melanocyte stimulating hormone (alphaMSH). Via their HS chains, syndecans potentiate the action of agouti-related protein and agouti signaling protein, endogenous inhibitors of alphaMSH. In wild-type mice, syndecan-3, the predominantly neural syndecan, is expressed in hypothalamic regions that control energy balance. Food deprivation increases hypothalamic syndecan-3 levels several-fold. Syndecan-3 null mice, otherwise apparently normal, respond to food deprivation with markedly reduced reflex hyperphagia. We propose that oscillation of hypothalamic syndecan-3 levels physiologically modulates feeding behavior.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / physiology
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Amino Acid Sequence
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Animals
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Blood Glucose / metabolism
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Corticosterone / blood
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Feeding Behavior / physiology*
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Female
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Fibroblast Growth Factor 2 / metabolism
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Food Deprivation
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Humans
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Hyperphagia / genetics
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Hyperphagia / physiopathology
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Hypothalamus / physiology*
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Insulin / blood
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Leptin / blood
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Male
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Mutagenesis
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Obesity / genetics
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Obesity / physiopathology
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Proteoglycans / chemistry
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Proteoglycans / deficiency
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Proteoglycans / genetics
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Proteoglycans / physiology*
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Receptors, Fibroblast Growth Factor / physiology
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Syndecan-1
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Syndecan-3
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Syndecans
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alpha-MSH / metabolism
Substances
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Blood Glucose
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Insulin
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Leptin
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Membrane Glycoproteins
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Proteoglycans
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Receptors, Fibroblast Growth Factor
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SDC1 protein, human
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SDC3 protein, human
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Sdc1 protein, mouse
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Sdc3 protein, mouse
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Syndecan-1
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Syndecan-3
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Syndecans
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Fibroblast Growth Factor 2
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alpha-MSH
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Corticosterone