Daily exercise is a low-cost treatment that improves metabolic health and protects against age-related diseases. However, many people are unable to perform an endurance exercise regimen due to illness, disability, advanced age or a work schedule that enforces sedentary behavior. Furthermore, humans have wide individual differences in their response to exercise. The genetic factors that cause this variance are not well understood. Here, we propose to use the fruit fly genetic model system to identify the causes of this variance. In the process, we will identify novel targets for therapeutic pharmaceuticals that can mimic the benefits of exercise in patients that are unable to complete an exercise program. Preliminary data strongly shows that activation of octopaminergic neurons during exercise is critical for inducing metabolic adaptations in muscle and fat. Furthermore, treatment with octopamine is capable of inducing exercise adaptations in sedentary flies. Here, we will identify which receptor or receptors are required for octopamine signaling to induce these benefits (Aim 1). Secondly, we will take advantage of sex-specific differences in exercise response in flies to identify the genetic differences that cause individual variation in response to daily exercise. These results will 1) inform the development of diagnostics to predict individual responses to exercise training, and 2) provide novel targets for therapeutics to provide the benefits of exercise to sedentary patients.
Daily endurance exercise is perhaps the best tool for preventive medicine yet discovered. It induces healthy metabolic adaptations and provides protection against heart disease, cancer, obesity, diabetes and dementia. However, many are either unwilling or unable to participate in regular exercise, due to illness, injury, advanced age, or other reasons. Furthermore, there is a great deal of individual variation in response to exercise. The genetic factors that cause this variability are not well understood. Here, we use the fruit fly model and its many powerful genetic tools to identify the essential genes that must be activated for exercise to have its effects. In doing so, we will come closer to identifying therapeutic targets for treatments to provide the benefits of exercise to those who are unable to complete an endurance training program.
| Sujkowski, Alyson; Spierer, Adam N; Rajagopalan, Thiviya et al. (2018) Mito-nuclear interactions modify Drosophila exercise performance. Mitochondrion : |
| Sujkowski, Alyson; Wessells, Robert (2018) Using Drosophila to Understand Biochemical and Behavioral Responses to Exercise. Exerc Sport Sci Rev 46:112-120 |
| Sujkowski, Alyson; Ramesh, Divya; Brockmann, Axel et al. (2017) Octopamine Drives Endurance Exercise Adaptations in Drosophila. Cell Rep 21:1809-1823 |
