Grant: Project Grant

As a risk factor for diabetes, cardiovascular disease, and cancer, obesity has been steadily increasing in society at alarming rates. Approximately 25% of Canadians are either over-weight or obese. Anti-obesity therapies have varying degrees of effectiveness, but no therapies actually target fat cells, which are key in the development of obesity. Fat cells, or adipocytes, grow through a complicated roadmap of signals that need precise direction. It is currently not known what are the proteins in fat cells that direct these signals needed for fat cell growth, but specialized proteins called molecular scaffolds could be the key players. One type of molecular scaffolds are 14-3-3 proteins, which we previously found to control the growth of fat cells in mice. We previously studied one member of 14-3-3 proteins, 14-3-3zeta, and mice that were genetically modified to have no 14-3-3zeta in all cells had less fat than normal mice. When mice were made to have more 14-3-3zeta in every cell, they actually gained more weight when fed food high in fat. It has been found that fat samples from obese individuals have higher levels of 14-3-3zeta. Combined with our mouse data, this raises the question of whether having more 14-3-3zeta in fat cells is enough to promote the development of obesity. Therefore, the aim of this proposal is to see if 14-3-3zeta can be a suitable target in the fat cell for treating obesity. This will be tested in mice that do not have 14-3-3zeta in their fat cells and to see if this protects them from developing obesity. Studies will also try to understand what 14-3-3zeta does in a fat cell and also if new drugs can be developed to block the actions of 14-3-3zeta in fat cells. Collectively, these studies will examine if 14-3-3zeta can be a suitable drug target to treat obesity, which continues to grow at alarming rates throughout the world.