Charting the Molecular Terrain of Exercise: Energetics, Exerkines, and the Future of Multiomic Mapping

Physical activity plays a fundamental role in human health and disease. Exercise has been shown to improve a wide variety of disease states, and the scientific community is committed to understanding the precise molecular mechanisms that underlie the exquisite benefits. This review provides an overview of molecular responses to acute exercise and chronic training, particularly energy mobilization and generation, structural adaptation, inflammation, and immune regulation. Furthermore, it offers a detailed discussion of known molecular signals and systemic regulators activated during various forms of exercise and their role in orchestrating health benefits. Critically, the increasing use of multiomic technologies is explored with an emphasis on how multiomic and multitissue studies contribute to a more profound understanding of exercise biology. These data inform anticipated future advancement in the field and highlight the prospect of integrating exercise with pharmacology for personalized disease prevention and treatment.