Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3.
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.
Reizes
O
O
Division of Newborn Medicine, Department of Pediatrics and Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. oreizes@go.com
Lincecum
J
J
Wang
Z
Z
Goldberger
O
O
Huang
L
L
Kaksonen
M
M
Ahima
R
R
Hinkes
M T
MT
Barsh
G S
GS
Rauvala
H
H
Bernfield
M
M
D000375:Aging / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005508:Food Deprivation; D006801:Humans; D006963:Hyperphagia / Q000235:genetics / Q000503:physiopathology; D007031:Hypothalamus / Q000502:physiology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D011509:Proteoglycans / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D053668:Syndecan-1; D053670:Syndecan-3; D053667:Syndecans; D000521:alpha-MSH / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; C508241:SDC1 protein, human; C508301:SDC3 protein, human; C508242:Sdc1 protein, mouse; C508302:Sdc3 protein, mouse; D053668:Syndecan-1; D053670:Syndecan-3; D053667:Syndecans; D016222:Fibroblast Growth Factor 2; D000521:alpha-MSH; D003345:Corticosterone