Regular parental exercise before mating influences offspring lower adiposity associated to hypothalamic neurodevelopmental changes

Physical inactivity is highly prevalent worldwide and affects not only individual health but also the health of future generations. However, the impact of parental physical activity, limited to the pre-mating period, on offspring body weight and composition remains poorly understood. Using a voluntary wheel running approach in mice, we uncovered that post-weaning offspring body weight and composition changes are modulated by the combined effects of pre-mating parental exercise and parental age. Notably, during lactation, pre-mating parental exercise reduced offspring visceral and subcutaneous adiposity, shortened tibia length in female offspring, and influenced offspring transcriptomic profiles of the hypothalamus, the central region regulating body weight and energy balance. These results highlight that regular pre-mating parental exercise may induce offspring neurodevelopmental changes. Although pre-mating exercise minimally impacted the expression of lactation-related genes in maternal subcutaneous fat, as well as breastmilk nutritional composition and miRNA content, these modest miRNA changes may nonetheless influence offspring hypothalamic regulation. Together, these data provide a comprehensive understanding of how parental age and pre-mating exercise impact post-weaning offspring body weight and composition and offer deeper insights into how regular pre-mating parental exercise influences offspring physiology during lactation.