%0 Figure %A Karlsson-Lindahl, Linda %A Schmidt, Linnéa %A Haage, David %A Hansson, Caroline %A Taube, Magdalena %A Egeciouglu, Emil %A Tan, Ying-xia %A Admyre, Therese %A Jansson, John-Olov %A Vlodavsky, Israel %A Li, Jin-Ping %A Lindahl, Ulf %A L. Dickson, Suzanne %D 2012 %T Proposed effects of heparanase on MC4R signaling. %U https://plos.figshare.com/articles/figure/_Proposed_effects_of_heparanase_on_MC4R_signaling_/333741 %R 10.1371/journal.pone.0034313.g005 %2 https://plos.figshare.com/ndownloader/files/663259 %K heparanase %K mc4r %X

HS chains of a cell-surface HSPG serve as co-receptors for AgRP, and at the same time preclude access of α-MSH to the MC4R. (Left panel) In the absence of heparanase (Hpa-ko) the HS chains remain intact, resulting in continuous AgRP-induced activation of MC4R, thus promoting food consumption, fat accumulation, and a positive energy balance. Under these conditions α-MSH signaling is severely restricted. (Right panel) HS chains are degraded by overexpressed heparanase (Hpa-tg), thus rendering the MC4R accessible to α-MSH, whereas AgRP devoid of its HS co-receptor is unable to engage the MC4R and thus remains inactive. This setting explains the acute effects of ICV-injected heparanase that lead to transient yet drastic reduction in feeding. However, it is also compatible with the long-term effects of transgenic heparanase expression that shift energy balance toward increased loss of body fat and compensatory up-regulation of appetite.

%I PLOS ONE