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Syndecan-3 modulates food intake by interacting with the melanocortin/AgRP pathway.
- Source :
-
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2003 Jun; Vol. 994, pp. 66-73. - Publication Year :
- 2003
-
Abstract
- Syndecan-3, expressed in the developing nervous system and adult brain, alters feeding behavior through its interaction with the CNS melanocortin system, which provides critical tonic inhibition of both food intake and body adipose stores. A variety of both in vitro and transgenic data supports the hypothesis that syndecan-3 modulates melanocortin activity via syndecan-3 facilitation of agouti-related protein (AgRP), a competitive antagonist of alpha-melanocyte-stimulating hormone (alpha-MSH) at the melanocortin-3 and -4 receptors. Consistent with this hypothesis, mice lacking syndecan-3, which therefore would be predicted to have less effective AgRP, are more sensitive to inhibition of food intake by the melanocortin agonist MTII. Additionally, we took advantage of the fact that syndecan-3 facilitation of AgRP is limited to when it is bound to the cell membrane. Pharmacologic inhibition of the enzyme that cleaves syndecan-3 from the cell membrane leads to increased food intake in fasted rats, which have elevated levels of AgRP. Furthermore, the shedding process appears to be regulated under physiologic conditions, because a putative inhibitor of the shedding process, tissue inhibitor of metalloprotease-3 (TIMP-3), is increased by food deprivation. These observations contribute to the hypothesis that syndecan-3 regulation of melanocortin signaling contributes to the normal control of energy balance. Collectively, the data suggest that the modulation of melanocortin regulation of energy balance by syndecan-3 is modulated by the action of a TIMP-3-sensitive metalloprotease.
- Subjects :
- Agouti-Related Protein
Animals
Food Deprivation
Intercellular Signaling Peptides and Proteins
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases metabolism
Melanocyte-Stimulating Hormones agonists
Membrane Glycoproteins genetics
Mice
Mice, Knockout
Obesity metabolism
Proteoglycans genetics
Rats
Receptors, Corticotropin genetics
Receptors, Corticotropin metabolism
Receptors, Melanocortin
Syndecan-3
Tissue Inhibitor of Metalloproteinase-3 genetics
Tissue Inhibitor of Metalloproteinase-3 metabolism
alpha-MSH metabolism
Eating
Melanocyte-Stimulating Hormones metabolism
Membrane Glycoproteins metabolism
Proteins metabolism
Proteoglycans metabolism
Receptor, Melanocortin, Type 3
alpha-MSH analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0077-8923
- Volume :
- 994
- Database :
- MEDLINE
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 12851299
- Full Text :
- https://doi.org/10.1111/j.1749-6632.2003.tb03163.x