Grant: Project Grant

In Canada, >10 million people are affected by metabolic diseases associated with excess fat storage (e.g. cardiovascular disease, obesity). Approximately 40% more men suffer from diseases of fat storage than women and drugs used to treat abnormal fat metabolism often work better in one sex (e.g. fenofibrates); yet, knowledge of how men and women differ in fat storage is incomplete. While lifestyle and sex hormones contribute to sex differences in fat storage, therapies based on lifestyle changes are difficult to maintain, and sex hormone therapy has undesirable side effects in both sexes. The next step forward in developing better treatments for abnormal fat storage is to identify the genes that control fat storage in each sex. Targeted therapies will reduce the burden and cost of diseases associated with fat storage (currently >$20bn). My research is at the forefront of discovering genes that drive sex differences in fat storage using fruit flies as an innovative model. Importantly, the genes that regulate fat storage are the same in flies and humans, and our work has shown that sex differences in fat storage faithfully reproduce male-female differences in mammals. Thus the genes involved in sex differences in fat storage we identify in flies will advance our understanding of this problem in mammals. Our use of flies has allowed excellent progress in 18 months: we identified fat storage genes that are regulated differently between the sexes. We hypothesize that this regulation explains why the sexes differ in fat storage. The goal of our project is to discover which of these genes is essential for fat storage in each sex, and to understand how these genes are regulated differently in males and females. We will advance health-related knowledge by identifying a pool of genes that control sex differences in fat storage, providing an essential starting point for researchers to develop new therapies for tackling metabolic disease that will work in men and women.