SUN-110 The Role Of RasD2 In Metabolism And Obesity

RasD2 encodes for a small GTP-binding protein that was initially identified and studied for its highly enriched expression in the striatum, where its expression is regulated by thyroid hormone and dopamine. Subsequently RasD2 has been shown to also be expressed in other tissues, including pancreatic islets, kidney, and heart. Microarray analysis comparing gene expression of islets from C57BL/6J mice fed a high-fat diet (HFD) vs regular chow found that RasD2 expression was increased in islets of mice fed a HFD, and RasD2 expression has been shown to increase in response to various insulin secretagogues, like imidazoline and sulfonylurea. However the downstream effects of these changes in RasD2 expression have never been fully elucidated. The aim of this project is to more fully characterize the role of RasD2 in metabolism. C57BL/6J mice with deletion of RasD2 were fed HFD (45% kcal fat) or regular chow and compared to their WT littermates. Glucose homeostasis was assessed with intraperitoneal glucose tolerance test and body composition was measured using (1)H-Magnetic Resonance Spectroscopy. When fed a regular diet, RasD2 KO mice had slightly lower body weight, but had similar body composition and no significant change in glucose tolerance when compared to WT littermates. When fed HFD, RasD2 KO and WT mice both gained a similar amount of body weight and developed glucose intolerance, but KO mice had less fat, and a higher proportion of lean mass. Using QPCR and western blot, we showed that RasD2 is expressed in adipose tissue, and that RasD2 expression increases in 3T3-L1 cells during differentiate into adipocytes. These data suggest a role for RasD2 in regulates energy homeostasis and/or adipogenesis, which may prove to be an attractive target in the battle against obesity. Ongoing studies will elucidate a more detailed mechanism.