How to train your rodent: Recommendations for the preclinical study of exercise-induced benefits in metabolic...

Regular physical activity is fundamental in promoting health and longevity. Numerous studies highlight the beneficial effects of exercise on metabolic parameters, but uncovering the mechanisms underlying the complex cellular responses and adaptations remains challenging in humans. Thus, animal models, in particular rodent models, have been indispensable for unveiling the underlying biological responses to exercise. Studies with precise exercise designs and diverse genetic models are vital for uncovering mechanistic pathways and informing pharmacological and behavioral strategies to combat non-communicable chronic diseases. Despite decades of research, recommendations to design preclinical exercise interventions and to measure key metabolic exercise adaptations in rodents have yet to be established. To enhance animal-to-human translation and ensure reproducibility, exercise studies must be rigorously controlled. Here, we outline key experimental considerations in rodents, including protocol design, exercise modality, sex, age, housing temperature, and circadian rhythm, to guide best practices and promote standardization and translation in future preclinical exercise studies.