Exercise, weight loss, and changes in body composition in mice: phenotypic relationships and genetic architecture.

The regulation of body weight and composition is complex, simultaneously affected by genetic architecture, the environment, and their interactions. We sought to analyze the complex phenotypic relationships between voluntary exercise, food consumption, and changes in body weight and composition and simultaneously localize quantitative trait loci (QTL) controlling these traits. A large (n = 815) murine advanced intercross line (G(4)) was created from a reciprocal cross between a high-running line and the inbred strain C57BL/6J. Body weight and composition (% fat, % lean) were measured at 4, 6, and 8 wk of age. After measurements at 8 wk of age, mice were given access to running wheels, during which food consumption was quantified and after which body weight and composition were assessed to evaluate exercise-induced changes. Phenotypic correlations indicated that the relationship between exercise and overall change in weight and adiposity depended on body composition before the initiation of exercise. Interval mapping revealed QTL for body weight, % fat, and % lean at 4, 6, and 8 wk of age. Furthermore, QTL were observed for food consumption and changes in weight, % fat, and % lean in response to short-term exercise. Here we provide some clarity for the relationship between weight loss, reduction in adiposity, food consumption, and exercise. Simultaneously, we reinforce the genetic basis for body weight and composition with some independent loci controlling growth at different ages. Finally, we present unique QTL providing insight regarding variation in weight loss and reduction in adiposity in response to exercise.