Grant: Operating Grant

Obesity, which is caused by an imbalance between energy intake and expenditure, increases the risk of developing multiple disorders including insulin resistance, type 2 diabetes, dyslipidemias, cardiovascular diseases, and cancers. The excessive accumulation of adipose tissue in the obese is associated with elevated circulating fatty acids and pro-inflammatory cytokines. Together with nutrient excess, these molecules impair systemic glucose and lipid homeostasis by reducing the ability of the liver and the muscle to normally respond to insulin. Treating obesity through diet and exercise proves to be very difficult in the long term. Therefore, safe molecular strategies aimed at improving metabolism in peripheral tissues represent interesting approaches to treat obesity-related diseases. The mammalian target of rapamycin (mTOR) is a protein that senses nutrients and growth factors and regulate anabolic processes in various organs. Over the last decade, several groups have observed that mTOR activity is elevated in the tissues of obese humans/mice and contributes the promotion of insulin resistance and to the deterioration of glucose/lipid homeostasis. Recently, we have identified DEP domain containing mTOR-interacting protein (DEPTOR) as a protein that binds and inhibits mTOR. The role of DEPTOR in regulating tissue function and systemic glucose/lipid metabolism in the normal state or in obesity is unknown. Whether DEPTOR could affect the metabolic profile of the obese by modulating mTOR activity has never been tested. This research proposal aims to determine the implication of DEPTOR in controlling metabolism and to understand its role in the development of obesity-related metabolic disorders.