Does IRAP regulate glucose and fat metabolism?

Insulin‐regulated aminopeptidase, IRAP, is highly expressed in fat and skeletal muscle where is it found to accompany the insulin‐responsive glucose transporter, GLUT4. In the brain, this enzyme is found in brain regions involved in controlling appetite and food intake. In characterising the phenotype of the IRAP knockout mice, we observed that these mice, when placed on a Western high fat diet, were not susceptible to weight gain, in contrast to their wildtype controls. We postulate that IRAP plays a role in the absorption and deposition of fat and in the absence of IRAP (either with gene deletion or inhibition of its activity); the mice have impaired fat absorption and/or enhanced fat clearance. This project will investigate if the IRAP KO mice or mice treated with IRAP inhibitors are protected against the health complications associated with diet-induced obesity.