Change search
ReferencesLink to record
Permanent link

Direct link
Heparanase Affects Food Intake and Regulates Energy Balance in Mice
Show others and affiliations
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 3, e34313- p.Article in journal (Refereed) Published
Abstract [en]

Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.

Place, publisher, year, edition, pages
2012. Vol. 7, no 3, e34313- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-175859DOI: 10.1371/journal.pone.0034313ISI: 000303894900080OAI: diva2:533343
Available from: 2012-06-13 Created: 2012-06-13 Last updated: 2012-06-13Bibliographically approved

Open Access in DiVA

fulltext(313 kB)132 downloads
File information
File name FULLTEXT01.pdfFile size 313 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Tan, Ying-XiaLi, Jin-PingLindahl, Ulf
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 132 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 311 hits
ReferencesLink to record
Permanent link

Direct link