Grant: Environments, Genes and Chronic Disease - LOI

Today we are facing an obesity epidemic. This is occurring because genetic factors that increase our risk of obesity that were previously hidden are now being uncovered by our changing environment and lifestyles. Diets high in fat and sugar, reduced physical activity and increased stress are among the factors that have been implicated. The effects of many genetic factors that affect our risk of obesity are influenced by the environment. Thus understanding these interactions is key to our ability to find biological causes of obesity that we could then use to devise therapies to help treat or prevent it. In work with mice, we have previously found two genes that affect obesity. Interestingly, we found these two genes have a larger effect in male mice than in females and that their effect was significantly altered in mice experiencing stress. Depending on the situation, stress can either cause people to crave tasty "comfort foods" or cause one to lose their appetite. Our data suggest that variation in these genes alters the way stress affects body weight, or conversely that increased stress affects the way these genes impact obesity. The studies in this proposal seek to determine how these genes and stress interact, along with sex, to affect obesity and to test whether the same happens in humans. Drs. Clee (expert on obesity in mice) and Viau (expert on sex-differences and stress) will work together to understand this interaction in mice. Dr. Rideout will use her expertise in sex-differences in body fat in fruit flies to further understand the interaction. The same genes affected in the mice are found in flies, and flies offer the ability to use advanced genetic tools that allow us to quickly test parts of the pathway we are studying and to find new parts of the pathway that we can then test in the mice. Finally, Dr. Meyre will test whether the genes and pathway we have/will identified/y interact with various types of stress to affect human obesity in men and women.