The Metabolome of Drosophila Reveals Exercise-Induced Stress and Anti-Inflammatory Response

Exercise is a known remedy for metabolic disorders, including obesity and type II diabetes. In humans and some model organisms, exercise is classified into different types and intensities based on the mode of exercise and the devices used. Since Drosophila has emerged as a model for exercise research, several devices have been developed for exercise training. These devices vary in mechanisms of operation; for example, the Power Tower (PT) uses a repeated drop-and-hit mechanism, and the TreadWheel (TW) uses end-over-end rotation. This variation in mechanisms that trigger the negative geotaxis of flies could impact exercise outcomes, and it remains unclear how this variation drives the response of flies to exercise training. Stress is a known response to exercise in humans and mice. Stress in Drosophila can be induced by various conditions, including heat, cold, chemical exposure, and other environmental stressors, but there is little information on exercise-induced stress. It is also unclear whether different devices elicit distinct stress responses or whether the exercise-induced stress response is similar to other stress responses (e.g., thermal, chemical). To explore the effects of device, sex, and genotype on multiple metabolic pathways, we used an untargeted metabolomics approach to further elucidate the molecular mechanisms of exercise. As no studies have directly examined the exercise metabolome of Drosophila, this study is the first to explore the metabolome of flies post-exercise. Our results revealed that exercising on different devices elicits varying responses and reshapes the metabolome of flies. We also identified specific small compounds that may be linked to stress and inflammatory response more in the PT-exercised flies than in the TW-exercised flies. Overall, the exercise device effect interacted with sex effect and genotype, such that male and female flies have different metabolite compositions post-exercise on TW and PT.