The impact of exercise on protein levels in <i>Drosophila melanogaster</i>

Moderate exercise is recommended by health experts across the globe to maintain health. Exercise induces a range of physiological changes, often shifting body composition towards increased muscle mass. To investigate the genetic factors controlling exercise responses, particularly altered body composition, we measured protein levels, as a proxy for muscle mass, in 32 genetically distinct strains from the Drosophila melanogaster Genetic Reference Panel (DGRP) that underwent a 5-day exercise treatment. At baseline, the protein levels varied significantly across genotypes and between sexes. The effects of exercise on protein content also were highly variable: some strains showed increased levels, others decreased levels, and many strains showed no significant change. A genome-wide association study (GWAS) identified multiple loci linked to both baseline and exercise-induced protein levels, as well as the change in protein levels after exercise. Many of these loci are involved in morphogenesis, neuronal development, and cell signaling. Notably, there was no correlation between protein concentration and measures of activity levels or climbing speed, suggesting muscle mass and function may be regulated independently. A modest positive correlation between protein levels and lifespan was observed in exercise-treated females, but not in other groups. These findings highlight the complex, context-dependent genetic architecture underlying exercise responses and underscore the need to consider both genotype and sex in physiological exercise studies. The genes identified here provide targets for future work aimed at elucidating the molecular mechanisms of exercise response.