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Göteborgs universitets publikationer

Heparanase affects food intake and regulates energy balance in mice.

Författare och institution:
Linda Karlsson-Lindahl (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Linnéa Schmidt (Institutionen för neurovetenskap och fysiologi); David Haage (-); Caroline Hansson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Magdalena Taube (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Emil Egecioglu (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Ying-xia Tan (-); Therese Admyre (-); John-Olov Jansson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Israel Vlodavsky (-); Jin-Ping Li (-); Ulf Lindahl (-); Suzanne L. Dickson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
PloS one, 7 ( 3 ) s. e34313
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Agouti-Related Protein, metabolism, Animals, Body Composition, Body Weight, Crosses, Genetic, Dietary Fats, Eating, genetics, physiology, Energy Metabolism, genetics, Feeding Behavior, Female, Gene Expression Regulation, Enzymologic, Glucuronidase, pharmacology, Infusions, Intraventricular, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptor, Melanocortin, Type 4, genetics, metabolism, Signal Transduction, Syndecan-3, metabolism, alpha-MSH, metabolism
Postens nummer:
Posten skapad:
2013-04-05 14:37

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