10.1371/journal.pone.0034313.g005 Linda Karlsson-Lindahl Linda Karlsson-Lindahl Linnéa Schmidt Linnéa Schmidt David Haage David Haage Caroline Hansson Caroline Hansson Magdalena Taube Magdalena Taube Emil Egeciouglu Emil Egeciouglu Ying-xia Tan Ying-xia Tan Therese Admyre Therese Admyre John-Olov Jansson John-Olov Jansson Israel Vlodavsky Israel Vlodavsky Jin-Ping Li Jin-Ping Li Ulf Lindahl Ulf Lindahl Suzanne L. Dickson Suzanne L. Dickson Proposed effects of heparanase on MC4R signaling. Public Library of Science 2012 heparanase mc4r 2012-03-27 01:02:21 Figure https://plos.figshare.com/articles/figure/_Proposed_effects_of_heparanase_on_MC4R_signaling_/333741 <p>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. <i>(Left panel)</i> In the absence of heparanase (<i>Hpa-</i>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. <i>(Right panel)</i> HS chains are degraded by overexpressed heparanase (<i>Hpa-</i>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.</p>