Obesity has reached pandemic proportions and represents an important risk factor for metabolic liver diseases and diabetes. Recent studies have put emphasis on the critical role of a special class of small molecules, called microRNAs, in insulin resistance, hepatic diseases and diabetes. Among these microRNAs microRNA-21 is significantly deregulated with obesity and diabetes in peripheral organs such as the liver and the adipose tissue. These recent findings suggest that microRNA-21 may play an important role in these metabolic diseases. This hypothesis is further supported by our preliminary studies showing that microRNA-21 is an important factor involved in hepatic metabolic disorders occurring in obese mice.

The goal of this project is to investigate the prophylactic and therapeutic benefits of microRNA-21 targeting using genetic and pharmaceutical tools in order to prevent liver metabolic disorders and insulin resistance in obese mice. In parallel, the molecular mechanisms by which microRNA-21 promotes the development of liver diseases and insulin resistance with obesity will be investigated.

These studies should provide important insights into the therapeutic potential of targeting microRNA-21 to alleviate obesity-associated liver diseases, insulin resistance and diabetes. In addition, this project should also permit the pinpointing of new and potentially other drug susceptable molecules contributing to the development of insulin resistance and diabetes with obesity.