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A novel brain pathway involved in pathogenesis of obesity and type-2 diabetes

48 months
Approved budget:
Professor David Grattan
Dr Mohammed Rizwan
Associate Professor Alexander Tups
Professor Peter Shepherd
Health issue:
Proposal type:
Lay summary
New Zealand has high rates of obesity and its associated complications such as type-2 diabetes (T2D). Māori and Pacific people are disproportionately affected by these disorders, with the prevalence of T2D two to three times higher than Pakeha. Human genome-wide association studies suggest that genetic variations in the Wnt-signalling pathway might be involved in the pathogenesis of T2D. We have recently discovered that Wnt signalling is activated by feeding in adults specifically in regions of the brain involved in regulation of appetite and blood glucose. Genetic deletion of β-catenin, an effector of Wnt signalling, specifically from these brain regions in mice resulted in obesity and impaired glucose clearance. These data suggest that Wnt signalling in the brain plays an essential role in maintaining healthy metabolism. Here, we aim to determine the specific neuronal pathways mediating this effect of Wnt signalling, providing novel advances in our understanding of the mechanisms of obesity and T2D.