Modeling exercise using optogenetically contractible Drosophila larvae

The pathophysiological effects of a number of metabolic and age-related disorders can be prevented to some extent by exercise and increased physical activity. However, the molecular mechanisms that contribute to the beneficial effects of muscle activity remain poorly explored. Availability of a fast, inexpensive, and genetically tractable model for muscle activity and exercise will allow rapid identification and characterization of the molecular mechanisms that mediate the beneficial effects of muscle activity. Here, we report the development and characterization of an optogenetically-inducible muscle contraction (OMC) model in Drosophila larvae that we used to model acute exercise-like physiological responses. To characterize muscle-specific transcriptional responses to acute exercise, we performed bulk mRNA-sequencing, revealing striking similarities between acute exercise-induced genes in flies and those previously identified in humans. Our larval muscle contraction model opens a path for rapid identification and characterization of exercise-induced factors. Total RNA was extracted from larval cuticle preparations using a Qiagen RNAeasy mini prep kit as per the manufacturer’s instructions. RNAseq on mRNA-selected samples were performed by the Sulzberger Columbia Genome Center, Columbia University, using an Illumina HISEQ 2500 instrument.