Parent-of-origin effects on voluntary exercise levels and body composition in mice

Despite the health-related benefits of exercise, many people do not engage in enough activity to realize the rewards, and little is known regarding the genetic or environmental components that account for this individual variation. We created and phenotyped a large G₄ advanced intercross line originating from reciprocal crosses between mice with genetic propensity for increased voluntary exercise (HR line) and the inbred strain C57BL/6J. G ₄ females (compared to males) ran significantly more when provided access to a running wheel and were smaller with a greater percentage of body fat pre- and postwheel access. Change in body composition resulting from a 6-day exposure to wheels varied between the sexes with females generally regulating energy balance more precisely in the presence of exercise. We observed parent-of-origin effects on most voluntary wheel running and body composition traits, which accounted for 3-13% of the total phenotypic variance pooled across sexes. G4 individuals descended from progenitor (F₀) crosses of HR♀ and C57BL/6J♂ ran greater distances, spent more time running, ran at higher maximum speeds/day, and had lower percent body fat and higher percent lean mass than mice descended from reciprocal progenitor crosses (C57BL/6J♀ x HR♂). For some traits, significant interactions between parent of origin and sex were observed. We discuss these results in the context of sex dependent activity and weight loss patterns, the contribution of parent-of-origin effects to predisposition for voluntary exercise, and the genetic (i.e., X-linked or mtDNA variations), epigenetic (i.e., genomic imprinting), and environmental (i.e., in utero environment or maternal care) phenomena potentially modulating these effects.